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.

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.

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.

Arterial stiffness in chronic kidney disease: a modifiable cardiovascular risk factor? Purpose of review There is an inverse, graded relationship between worsening chronic kidney disease (CKD) and increasing cardiovascular risk independent of traditional cardiovascular risk factors. Increasing arterial stiffness is a powerful predictor of cardiovascular outcomes in CKD. Developing novel therapeutic strategies to reverse this process is an attractive concept. This review presents the results of a literature survey of the last 18 months to establish if arterial stiffness can be considered a reversible cardiovascular risk factor in patients with CKD. Recent findings Multiple potential therapeutic approaches to reduce arterial stiffness have been proposed and tested. However, arterial stiffness and blood pressure (BP) have a very close bidirectional relationship. Any change in BP will have an effect on arterial stiffness and vice versa. At present, there is no robust evidence to support the notion that arterial stiffness can be considered reversible other than as a direct consequence of reduction in BP. Summary For now, arterial stiffness should be considered an indirectly modifiable cardiovascular risk factor through optimal control of BP. Measures of arterial stiffness should be regarded as research and risk stratification tools rather than a therapeutic target in itself.

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.

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).

Acute kidney injury prediction models: current concepts and future strategies Purpose of review Acute kidney injury (AKI) is a critical condition associated with poor patient outcomes. We aimed to review the current concepts and future strategies regarding AKI risk prediction models. Recent findings Recent studies have shown that AKI occurs frequently in patients with common risk factors and certain medical conditions. Prediction models for AKI risk have been reported in medical fields such as critical care medicine, surgery, nephrotoxic agent exposure, and others. However, practical, generalizable, externally validated, and robust AKI prediction models remain relatively rare. Further efforts to develop AKI prediction models based on comprehensive clinical data, artificial intelligence, improved delivery of care, and novel biomarkers may help improve patient outcomes through precise AKI risk prediction. Summary This brief review provides insights for current concepts for AKI prediction model development. In addition, by overviewing the recent AKI prediction models in various medical fields, future strategies to construct advanced AKI prediction models are suggested.

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.

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.