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.

Urgent-start peritoneal dialysis: is it ready for prime time? Purpose of review This review aims to provide an up-to-date summary of the definition, current practice and evidence regarding the role of urgent-start peritoneal dialysis (USPD) in patients with end-stage kidney disease who present with unplanned dialysis requirement without functional access. Recent findings USPD can be broadly defined as peritoneal dialysis initiation within the first 2 weeks after catheter insertion. Published practice patterns, in terms of catheter insertion approach, peritoneal dialysis initiation time or initial fill volume, are highly variable. Most evidence comes from small, retrospective, single-center observational studies and only one randomized controlled trial. Compared with conventional-start peritoneal dialysis, USPD appears to moderately increase the risk of mechanical complications, such as dialysate leak (relative risk 3.21, 95% confidence interval 1.73–5.95), but does not appear to adversely affect technique or patient survival. USPD may also reduce the risk of bacteremia compared with urgent-start hemodialysis delivered by central venous catheter (CVC). Summary USPD represents an important opportunity to establish patients with urgent, unplanned dialysis requirements on a cost-effective, home-based dialysis modality with lower serious infection risks than the alternative option of hemodialysis via CVC. Robust, well executed trials are required to better inform optimal practice and safeguard patient-centered and patient-reported outcomes. Correspondence to David W. Johnson, MBBS, MD, PhD, Professor, Department of Nephrology, Level 2, ARTS Building, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Brisbane, QLD 4102, Australia. Tel: +61 7 3176 5080; fax: +61 7 3176 5480; e-mail: david.johnson2@health.qld.gov.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Bariatric surgery as a renoprotective intervention Purpose of review Through its direct adverse effects on the kidney and via associated intermediate disease states like type 2 diabetes and hypertension, obese has arguably become the master risk factor for chronic kidney disease (CKD). The purpose of this review is to critically evaluate bariatric surgery, which is the most effective weight reduction strategy available, as a renoprotective strategy. Recent findings Recent randomized studies confirm that bariatric surgery is effective at improving or even remitting major CKD risk factors such as type 2 diabetes and hypertension. In addition, observational studies performed primarily in patients without preexisting CKD report improvements in estimated glomerular filtration rate and albuminuria after bariatric surgery. Yet this literature is limited by study design, participant selection, statistical power, and measurement issues that must be overcome to better define kidney-related benefits, especially with regard to harder kidney-related and other clinical endpoints. Summary Encouraging data exist on the renoprotective effects of bariatric surgery. However, important knowledge gaps still remain. Future research should focus on studying, ideally in randomized fashion, the renoprotective effects of bariatric surgery in patients with preexisting CKD to better define the benefit–risk ratio for each patient. Correspondence to Allon N. Friedman, 550 University Blvd., Suite 6100, Indianapolis, IN 46202, USA. Fax: +1 317 948 9419; fax: +1 317 944 4319; e-mail: allfried@iu.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

In-vivo techniques for determining nephron number Purpose of review Many studies have suggested low nephron endowment at birth contributes to the risk of developing hypertension and chronic kidney disease (CKD) later in life. Loss of nephrons with age and disease is largely a subclinical process. New technologies are needed to count nephrons as glomerular filtration rate (GFR) is a poor surrogate for nephron number. Recent findings Cortical volume, glomerular density, and percent globally sclerotic glomeruli are imperfect surrogates for nephron number. The disector–fractionator method is the most accurate method to count nephrons but is limited to autopsy settings. Glomerular density combined with kidney imaging and ultrafiltration coefficient-based methods require a kidney biopsy, and have been applied in living humans (kidney donors). Low nephron number predicts a higher postdonation urine albumin. Contrast-enhanced MRI has detected glomeruli without a biopsy, but so far, not in living humans. Summary Currently, there is no accurate and well tolerated method for determining nephron number in living humans. A clinically useful method may allow GFR to be replaced by its more relevant determinants: nephron number and single nephron GFR. This could revolutionize nephrology by separating the measurement of chronic disease (nephron loss) from more reversible hemodynamic effects (nephron hyperfiltration/hypofiltration). Correspondence to Andrew D. Rule, Mayo Clinic 200 1st St SW, Rochester, MN 55905, USA. Tel: +1 507 266 1045; fax: +1 507 266 7891; e-mail: rule.andrew@mayo.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Current opinions in nephrology and hypertension: kidney transplantation in patients with plasma cell dyscrasias Purpose of review Plasma cell dyscrasias encompass a group of hematological disorders characterized by increased production of immunoglobulins by clonal B cells. Kidney involvement is common. Significant advances in the treatment of plasma cell dyscrasias have resulted in improved survival and may permit kidney transplantation in candidates previously denied transplantation. Treatments may also have effects on kidney transplant recipients who develop plasma cell dyscrasias post transplantation. Recent finding The available evidence suggests that transplantation of candidates with nonmultiple myeloma plasma cell dyscrasias provides good outcome with low recurrence rates, so long as the disease has been treated with a complete or good partial response prior to transplantation. Candidates with a history untreated MGRS or a history of multiple myeloma have a high rate of recurrence posttransplant. Kidney transplant recipients who develop plasma cell dyscrasias post transplantation have an increased risk of death and thalidomide-based regimens may increase the risk of rejection. Summary Transplant candidates with a history of plasma cell dyscrasia who are in remission should not be excluded from transplantation. Individuals with multiple myeloma have a high rate of recurrence and myeloma post kidney transplant must be managed carefully. Correspondence to Erik L. Lum, MD, Connie Frank Kidney Transplant Center, 200 Medical Plaza, Ste 565, Los Angeles, CA 90095, USA. Tel: +1 310 267 0552; e-mail: elum@mednet.ucla.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Hemodialysis care for undocumented immigrants with end-stage renal disease in the United States Purpose of review Across the United States, significant variation exists in the provision of care of undocumented immigrants with end-stage renal disease (ESRD), with some states providing standard dialysis, and other states providing emergency-only hemodialysis (EoHD). Recent findings EoHD is associated with higher morbidity and mortality compared with standard hemodialysis. EoHD is also associated with higher healthcare utilization, resulting in more emergency department visits, more days spent in the hospital, and higher healthcare costs. Undocumented immigrants with ESRD who rely on EoHD also experience crippling and potentially fatal physical symptoms as well as psychosocial suffering, with some patients describing recurrent near-death experiences. Clinicians who provide EoHD to undocumented patients report experiencing moral distress and symptoms of professional burnout because of providing care that they perceive as unethical and far below the standard of care. Summary Undocumented immigrants with ESRD who rely on EoHD have worse health outcomes and quality of life compared with patients who receive standard hemodialysis. EoHD is also more costly to the healthcare system. Healthcare policy reform is critical as more research demonstrates the worse clinical outcomes and higher costs of EoHD. Correspondence to Lilia Cervantes, MD, Department of Medicine, Denver Health and Hospital Authority, 601 Broadway, MC 4000, Denver, CO 80204-4507, USA. Tel: +1 303 602 5075; e-mail: Lilia.Cervantes@ucdenver.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Can incremental haemodialysis reduce early mortality rates in patients starting maintenance haemodialysis? Purpose of review Early mortality rates after the start of maintenance haemodialysis therapy are high. Compared with three-times weekly haemodialysis, incremental haemodialysis is associated with better preservation of residual renal function (RRF) and at least equivalent mid-term to long-term survival. However, there is paucity of data in relation to its use as a means of helping patients through the transitional period, when they first become dialysis dependent. Recent findings Studies of incremental haemodialysis have overlooked early mortality as an outcome measure. This is primarily due to their retrospective design which makes it difficult to link early deaths to the frequency of haemodialysis. New data confirm previous observations associating incremental haemodialysis with favourable outcomes. They also raise the possibility that in selected groups and for short periods, the pursuit of set clearance targets during the early days of dialysis may not necessarily bring additional short-term gains. Summary We argue that, while simpler ways of estimating RRF are being explored, future trials must consider implementing incremental haemodialysis focusing on practical aspects of care in the transitional period; safety monitoring in such regimes should be undertaken using conventional methods. Such an approach is likely to benefit a larger subset of haemodialysis population. Correspondence to Dr Adil M. Hazara, Academic Renal Research, 2nd Floor Alderson House, Hull Royal Infirmary, Anlaby Road, Kingston upon Hull HU3 2JZ, UK. Tel: +44 1482 605260; fax: +44 1482 605256; e-mail: adilhazara@nhs.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Assessing the health of the nephron in acute kidney injury: biomarkers of kidney function and injury Purpose of review Serum creatinine and urine output continue to be the mainstays of diagnosis of acute kidney injury, though both of these measures have significant limitations, especially in acutely hospitalized patients. Biomarkers in both blood and urine have been studied extensively in the research setting and are on the verge of clinical practice to improve diagnosis of AKI. Recent findings Blood and urine biomarkers can be localized to specific areas or functions within the nephron. Biomarkers can help to characterize glomerular or tubular function; glomerular, tubular, or interstitial injury; inflammation; or repair. Further, biomarkers can improve diagnosis of AKI in various clinical settings including acute interstitial nephritis, acute tubular injury, and hepatorenal syndrome, and cardiorenal syndrome. Summary Biomarkers are becoming more prevalent in both research and getting close to clinical use. Both blood and urine biomarkers can help to localize impairment in nephron health by either location or function within the nephron and among various causes of AKI. Correspondence to Chirag R. Parikh, MD, PhD, Director, Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E Monument St, Ste 416, Baltimore, MD 21287, USA. Tel: +1 410 955 5268; e-mail: chirag.parikh@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.