Influenza in dialysis patients: an opportunity to decrease mortality? Purpose of review Influenza is a major cause of morbidity in dialysis patients. Recent findings A recent meta-analysis finds reduced influenza infections, hospitalizations and deaths with use of high dose as compared with standard-dose vaccine in the elderly. There remain no randomized clinical trials of vaccine efficacy in dialysis patients. One observational study finds reduced all-cause hospitalization with high-dose as compared with standard-dose vaccine but another study finds no difference in influenza related events. A simulation study, in which the timing of vaccination and antibody waning rates are varied, finds vaccine efficacy among populations prone to premature waning, to be greater if the vaccine is administered later, as long as the opportunity to vaccinate does not decline. In a phase 3 trial involving low-risk patients with uncomplicated influenza, baloxavir (which is of a novel class of antiinfluenza treatment), was associated with a faster decline in virus titers and no difference in resolution of symptoms as compared with oseltamivir. Summary By extension of high-quality evidence in the elderly, we recommend using the high dose vaccine in all dialysis patients. Vaccine efficacy may be enhanced in dialysis patients if vaccination is delayed until late October to mid-November. It is premature to use baloxavir over oseltamivir or the combination to treat influenza in dialysis patients though trials are forthcoming. Correspondence to Dana C. Miskulin, MD, Division of Nephrology, Tufts Medical Center, 800 Washington St. Box 391, Boston, MA 02111, USA. Tel: +1 617 636 9936; fax: +1 617 636 8329; e-mail: dmiskulin@tuftsmedicalcenter.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Vaccination for the postkidney transplant population Purpose of review Kidney transplant recipients are at high risk of contracting infections, some of which are considered vaccine-preventable, because of their highly immunosuppressed state. In this vulnerable group of patients, infection can lead to poor outcomes including graft failure and death, thus vaccination in the posttransplant population is an important strategy in order to mitigate this risk. The present review is aimed at providing an update on recent advances with respect to vaccination strategies in kidney transplant recipients. Recent findings General principles behind vaccination in kidney transplantation have remained consistent over many years. More recently, efforts have been focused on developing newer strategies for vaccination against influenza and herpes zoster in organ transplant recipients. Newer data on the immunogenicity of vaccines directed against pneumococcal disease, human papillomavirus, and hepatitis B virus in kidney transplant recipients have become available and will also be discussed in the present review. Summary Kidney transplant recipients are highly-vulnerable to contracting serious infections by way of their immunosuppressed state and their dampened ability to mount an immunogenic response to vaccines. Thus, ongoing advances in vaccination strategies in this group of patients should be an important area of focus of future research in order to help promote healthier living and greater survival postkidney transplant. Correspondence to Deepali Kumar, 585 University Avenue, 11-PMB-174, Toronto, ON M5G 2N2, Canada. Tel: +1-416-340-4241; e-mail: Deepali.kumar@uhn.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Interventions for improving outcomes in acute kidney injury Purpose of review Since the adoption of the classification of acute kidney injury (AKI) through changes in serum creatinine and/or urine output, much data have accumulated as to the associated risks in terms of morbidity and mortality after the development of AKI. However, until recently, a nihilistic approach persisted which implied that little could be done to alter the clinical course of a patient with AKI even where early identification was achieved. This view is reinforced by the opinion that given the broad cause underlying the syndrome of AKI, a ‘one size fits all’ approach is unlikely to be successful. Recent findings Recent evidence suggests that the management of AKI may be improved somewhat by simple measures, such as the use of care bundles particularly in the intensive care setting. Moreover, there are other interventions using common treatments, which may prove to be of benefit as well as some early evidence that specific therapeutics may be on the horizon. Summary Although a syndrome of significantly differing causes, the application of standardized care bundles appears promising and this approach may be improved by the use of specific therapies, including recombinant alkaline phosphatase, the use of intravenous bicarbonate and remote ischaemic preconditioning may also ameliorate the effects of AKI. Correspondence to Lui G. Forni, Department of Intensive Care Medicine, Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK. Tel: +44 1483 571122; xt 4057; e-mail: luiforni@nhs.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Prolyl-hydroxylase inhibitors for the treatment of anemia in chronic kidney disease Purpose of review Prolyl-hydroxylase inhibitors are a novel class of orally administered drugs that are under development for the treatment of anemia in patients with chronic kidney disease. This review discusses the biology of these drugs and their target – hypoxia-inducible factor and potential advantages and disadvantages of these therapies. Finally, we will discuss current trials in patients with both chronic kidney disease and end-stage renal disease. Recent findings Recent smaller studies have found that prolyl-hydroxylase are as effective as erythropoietin in treating anemia of chronic kidney disease. We do not yet know if they have the same cardiovascular and cancer-related risk profile and these questions will be answered by large phase III trials that are ongoing. Summary Although prolyl hydroxylase inhibitors have much potential, questions remain regarding their efficacy and safety. Should these concerns prove to be unfounded, the treatment of anemia in chronic kidney disease will likely be transformed over the next decade. Correspondence to Gearoid M. McMahon, MB BCh, Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA. Tel: +1 17 999 7876; e-mail: gmmcmahon@bwh.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

New treatments for cytomegalovirus in transplant patients Purpose of review The purpose of this review is to highlight novel advances in prophylaxis against and treatment of CMV in kidney transplant recipients. Current options include intravenous ganciclovir and oral valganciclovir, but use of these agents is limited by side effects, such as myelosuppression as well as evolving resistance in CMV strains. Recent findings Advances in the field include novel drugs that have shown promise in preliminary studies and are now being tested in large-scale clinical trials. Moreover, there is a developing focus in enhancing host immune responses to better protect against viral infection using anti-CMV vaccines. Studying host immune responses to CMV has also led to improved monitoring strategies, such as the QuantiFERON assay, which will allow for improved risk stratification and targeted therapies in transplant recipients. Summary In summary, although options for prophylaxis and treatment against CMV have been somewhat limited to date, a number of new strategies are currently under development with several drugs in phase 3 trials. Therefore, the landscape of CMV management in kidney transplant recipients will be changing significantly in the coming years with the ultimate goal of safer and more effective therapies to combat CMV. Correspondence to Emily Blumberg, MD, Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Tel: +1 215 662 6932; e-mail: blumbere@pennmedicine.upenn.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

When are you too old to get a kidney transplant? Purpose of review With the increasing incidence and prevalence of ESRD in the elderly, we are now transplanting more elderly patients. Although we know from previous reports that transplantation provides increased survival advantage and/or quality of life when compared to being on dialysis, we also know that transplantation is not the best option for all patients. In this review, we try to identify the upper age limit (if any) for deceased donor renal transplantation, predictive factors that can identify the risks for transplant outcomes, frailty, and immunosenescence. Recent findings Review of data over the last 5 years have identified certain risk predictors and outcomes that might be helpful in evaluation of the elderly transplant recipient, which we aim to summarize in this review. Summary Identifying predictors to risk stratify elderly patients and promote transplantation is much needed. Modifiable risks should be addressed to ensure more candidates become transplantable. A combination of physical, medical, and immunological markers to better identify recipients is imperative for future research gearing towards precision medicine. Correspondence to Dr Lavanya Kodali, 5779 E Mayo Blvd, Phoenix, Arizona, USA. Tel: +1 480 342 4745; fax: 1 480 342 3033; e-mail: kodali.lavanya@mayo.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Skin autofluorescence: an emerging biomarker in persons with kidney disease Purpose of review Skin autofluorescence (SAF) is a measure of the accumulation of advanced glycation end-products (AGEs) proposed to act as a marker of ‘cumulative metabolic stress’. This article discusses mechanisms of AGE formation and reviews published literature on SAF as a biomarker and risk factor across the spectrum of kidney disease. Recent findings SAF is elevated in adults and children on dialysis. Higher SAF is an independent risk factor for cardiovascular and all-cause mortality in persons receiving haemodialysis and for all-cause mortality in persons performing peritoneal dialysis, though the increase in discrimination when SAF was added to traditional risk factors was modest. In less advanced chronic kidney disease, higher SAF predicts all-cause mortality and progression. SAF is elevated in renal transplant recipients, but to a lesser extent than in dialysis patients. In one study, higher SAF predicted graft loss and mortality. SAF has been reported to be increased in patients with acute kidney injury. Summary A growing body of evidence attests that SAF, a marker of AGE accumulation, is a risk factor for mortality and kidney function decline in multiple types of kidney disease. Further studies are warranted to evaluate interventions to reduce SAF and the impact on clinical outcomes. Correspondences to Maarten W. Taal, MBChB, MMed, MD, FCP(SA), FRCP, Department of Renal Medicine, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, Uttoxeter Road, Derby DE22 3NE, UK. Tel: +44 1332 789344; e-mail: maarten.taal1@nhs.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Risk prediction in chronic kidney disease Purpose of review Accurate risk stratification in patients with chronic kidney disease (CKD) is highly desirable to help guide earlier, targeted treatment in high-risk individuals. In this review, we report recent developments in our understanding of risk factors and risk prediction in patients with CKD. Recent findings A large meta-analysis has shown that conventional cardiovascular risk factors continue to play an important role in disease progression and adverse outcomes in patients with advanced CKD where the estimated glomerular filtration rate (eGFR) is < 30 ml/min/1.73 m2). Several studies have shed light on novel biomarkers in CKD, including peptides (LG1 M), genes (MUC1) and metabolic factors (urinary oxalate excretion). Cortical oxygenation measured by BOLD-MRI also provides a novel radiological measure predictive of future eGFR decline. A new risk prediction score for patients with CKD G4-5 has been developed, offering an aid to decision-making in these patients. Summary Ongoing work across various disciplines continues to unravel the determinants of CKD progression. A few notable risk prediction tools in CKD have now surfaced but whether they can be utilised to offer improved care remains a key unanswered question. Correspondence to Ibrahim Ali, Department of renal medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK. Tel: +44 0161 789 7373; fax +44 0161 206 5713; e-mail: ibrahim.ali@srft.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Thyroid disease in end-stage renal disease Purpose of review Hypothyroidism is a highly prevalent endocrine disorder in the end-stage renal disease (ESRD) population, yet many cases may remain latent and undiagnosed. Recent findings Epidemiologic data show that there is a nearly five-fold higher prevalence of hypothyroidism in advanced chronic kidney disease (CKD) patients vs. those without CKD. Given that the metabolism, degradation, and excretion of thyroid hormone and its metabolites, as well as the regulation of the hypothalamic–pituitary–thyroid axis may be altered in ESRD, certain considerations should be made when interpreting thyroid functional tests in these patients. Growing evidence shows that hypothyroidism and other thyroid functional test derangements are associated with higher risk of cardiovascular disease, worse patient-centered outcomes, and survival in the advanced CKD population, including those with ESRD. Although limited data examining treatment of hypothyroidism suggests benefit, further studies of the efficacy and safety of thyroid hormone supplementation, including clinical trials and rigorous longitudinal observational studies are needed to inform the management of thyroid dysfunction in CKD. Summary Given the high burden of hypothyroidism in ESRD patients, and potential ill effects on their cardiovascular health, patient-centered outcomes, and survival, further research is needed to inform the optimal management of thyroid dysfunction in this population. Correspondence to Connie M. Rhee, MD, MSc, Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine School of Medicine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, USA. Tel: +1 714 456 5142; fax: +1 714 456 6034; e-mail: crhee1@uci.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Change in albuminuria as a surrogate endpoint Purpose of review Chronic kidney disease is a global health problem with few effective therapies available that slow the progression to end-stage renal disease. The established clinical endpoints for renal trials; doubling of serum creatinine or end-stage renal disease, are late manifestations of CKD. This leads to large trials enrolling preferably patients with advanced stages of CKD. The use of valid surrogate biomarkers that substitute a clinical endpoint (surrogate endpoints), can lead to trials of shorter duration that can be performed at earlier stages of CKD. Change in albuminuria has been proposed as surrogate endpoint in CKD. Yet, although albuminuria is a strong risk factor for CKD progression, there is persistent uncertainty about its validity to substitute clinical endpoints. Recent findings New observational studies have demonstrated robust associations between changes in albuminuria and risk of end-stage renal disease. In addition, a meta-analysis of observational studies confirmed the strong association between change in albuminuria and end-stage renal disease. Another meta-analysis of clinical trials showed moderately strong associations between treatment effects on albuminuria and treatment effects on clinical endpoints. These new data support a role for change in albuminuria as surrogate endpoint for clinical trials of progression of CKD. Summary There is increasing evidence that change in albuminuria is a valid surrogate endpoint for CKD. Implementing albuminuria as surrogate requires proper understanding of the settings in which the surrogate works well. Correspondence to Dr Hiddo J.L. Heerspink, Professor, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, the Netherlands. Tel: +31 50 361 7859; e-mail: h.j.lambers.heerspink@umcg.nl Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.