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Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients. Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index. Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients. Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients. • Among ESRD patients, 25(OH)D concentrations followed seasonal variation during two consecutive years. • 25(OH)D concentrations were higher in the summer and lower in the winter time with a peak-trough difference of 3.2 ng/mL. • 25(OH)D concentrations increased steadily by 1.3 ng/mL/year. • IPTH, ALP and calcium concentrations also showed seasonal variation in contrast to phosphorus concentrations. • Clinicians and researchers should be aware of these variations when interpreting laboratory results in dialysis patients. [ABSTRACT FROM AUTHOR]

Launched in 2016, the overarching goal of the Precision Medicine Initiative is to promote a personalized approach to disease management that takes into account an individual's unique underlying biology and genetics, lifestyle, and environment, in lieu of a one-size-fits-all model. The concept of precision medicine is pervasive across many areas of nephrology and has been particularly relevant to the care of advanced chronic kidney disease patients transitioning to end-stage kidney disease (ESKD). Given many uncertainties surrounding the optimal transition of incident ESKD patients to dialysis and transplantation, as well as the high mortality rates observed during this delicate transition period, there is a pressing urgency for implementing precision medicine in the management of this population. Although the traditional paradigm has been to commence incident hemodialysis patients on a 3 times/week treatment regimen, largely driven by adequacy targets, there has been growing recognition that alternative treatment regimens (ie, incremental hemodialysis) may be preferred among certain subpopulations when taking into consideration factors such as patients' residual kidney function, volume status fluctuations, symptoms, and preferences. In this review, we examine the origins of current practices in how dialysis is initiated among incident ESKD patients; incremental dialysis therapy as a dynamic and patient-centric approach that is tailored to patients' unique characteristics; recent data on the incremental hemodialysis regimen and outcomes; and future research directions using a precision nephrology approach to ESKD management with the potential to develop novel approaches, tools, and collaborative efforts to improve the health, well-being, and survival of this population. [ABSTRACT FROM AUTHOR]

In the general population, elevated triglyceride (TG) levels are an important risk factor for cardiovascular disease and mortality. However, in chronic kidney disease, the association of serum TGs with mortality is less clear. We sought to examine the association of TGs with mortality across chronic kidney disease (CKD) stages in a large cohort of U.S. veterans. We examined 2,086,904 U.S. veterans with a TG measurement obtained between a baseline period of October 2004 and September 2006, with follow-up until December 2014 (median [interquartile range {IQR}]: 9.2 [6.5, 9.9] years). Associations of TGs with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models. Patients were 64 ± 14 years old with a median (IQR) baseline TG of 129 [88, 193] mg/dL and estimated glomerular filtration rate of 76 [61, 91] mL/min/1.73 m2. More advanced CKD was associated with higher odds of TGs ≥ 240 mg/dL. Low levels of TGs < 80 mg/dL were associated with a higher risk of mortality across all stages, whereas TG levels ≥ 240 mg/dL were only associated with a higher risk of all-cause mortality in non-CKD and CKD stages 3A, 3B, and 4 (reference: TG 120 to <160 mg/dL). The relationship of higher TGs with mortality incrementally attenuated across worsening stages of CKD and attenuated to the null among patients with CKD stage 5/end-stage renal disease. Similar results were observed for cardiovascular mortality, in strata by age and diabetes, and further adjustment for high-density lipoprotein and low-density lipoprotein. Associations of elevated TGs with all-cause and cardiovascular mortality were incrementally attenuated across more advanced stages of CKD. • Odds of having greater triglycerides increase across worsening kidney disease. • The higher triglyceride mortality risk declines across worsening kidney disease. • Results are similar in diabetics and nondiabetics and the elderly and nonelderly. [ABSTRACT FROM AUTHOR]

Among kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. Historical cohort study. We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011. We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis. Among 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate. Among very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dietary acid reduction with fruits and vegetables or sodium bicarbonate reduces kidney injury in subjects with moderately reduced GFR due to hypertensive nephropathy," by Nimrit Goraya and colleagues in the 2012 issue.

The combination of serum 25-hydroxyvitamin D (25D) and fibroblast growth factor 23 (FGF23) levels predict hard renal outcomes in patients with chronic kidney disease (CKD), independent of classical markers of mineral and bone disorders, including serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D levels, and active vitamin D therapy. In a prospective cohort study of 738 Japanese pre-dialysis outpatients with CKD, we examined potentially non-linear associations between 25D and FGF23 levels and estimated glomerular filtration rate (eGFR) changes in 727 patients with at least a 6-month observation period and no history of admission by acute kidney injury. We used multiple regression analyses with restricted cubic spline functions using annualized eGFR decline as a dependent variable. A significantly non-linear positive relationship between 25D and eGFR changes was observed. The annualized eGFR decline was greater in patients with 25D concentrations <25 and 23 ng/ml in univariate and multivariate analyses, respectively. Above this threshold, the eGFR decline plateaued. FGF23 showed a linear negative association with eGFR changes. After dividing the patients into four groups according to median 25D and FGF23 levels, the annualized eGFR changes in the Low FGF23-Low 25D, High FGF23-High 25D, and High FGF23-Low 25D groups were 0.49 (95% confidence intervals: −2.83 to 3.81), −1.24 (−5.00 to 2.52), −4.77 (−8.85 to −0.69), respectively, relative to the Low FGF23-High 25D group (P for trend, 0.02). Thus, combined use of FGF23 and 25D is useful to predict eGFR change in patients with CKD as well as hard renal outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Low 25-hydroxyvitamin D (25D), increased levels of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were reported to be risk factors for mortality in chronic kidney disease (CKD). However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD. Methods: In this prospective cohort study, we enrolled 738 predialysis outpatients in the two nephrology departments. We employed Cox proportional hazards analyses to elucidate predictors of the endpoint, defined as fatal or non-fatal cardiovascular event requiring hospitalization. Multiple imputation was performed for missing values. Results: Mean estimated glomerular filtration rate (eGFR) was 35mL/min/1.73m2. During a median duration of 4.4years, 86 patients developed the endpoint, of whom 62 patients achieved it before the initiation of dialysis. Multivariable analyses revealed that high serum intact FGF23 levels predicted the outcome preceding dialysis initiation (hazard ratio (HR) per lnFGF23 (SD), 1.64 (1.27–2.30)), while 25D, PTH, and bone-specific ALP did not. Adding FGF23 to the conventional model of age, sex, diabetes, prior CVD, pulse pressure, and eGFR, led to a net reclassification improvement of 6.87% (P =0.04). Not censoring the patients at the start of dialysis and continuing follow-up even after dialysis, FGF23 levels did not predict the outcome (HR, 1.16 (0.91–1.48)). Complete case analyses yielded similar results. Conclusions: Intact FGF23 levels in predialysis CKD predicted incident cardiovascular events requiring hospitalization before starting dialysis, but did not predict events during the entire follow-up period, including post dialysis initiation. [Copyright &y& Elsevier]