A 6-Month clinical practice pilot study of sucroferric oxyhydroxide on nutritional status in patients on peritoneal dialysis.

BACKGROUND: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. METHODS: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. RESULTS: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. CONCLUSION: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. TRIAL REGISTRATION: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.

Fibroblast Growth Factor 23 Trajectories in Chronic Hemodialysis Patients: Lessons from the HEMO Study.

BACKGROUND: Long-term patterns of fibroblast growth factor 23 (FGF23) are poorly characterized among dialysis patients. OBJECTIVES: To identify different FGF23 trajectories and determine clinical factors that predict distinct FGF23 trajectories and whether FGF23 trajectories differ in regard to their associations with all-cause mortality among prevalent hemodialysis patients. METHODS: The HEMO study was a randomized multicenter study evaluating the effects of high-dose vs. standard-dose and high-flux vs. low-flux hemodialysis on mortality. We measured intact FGF23 levels in stored serum samples at baseline and annually among 919 HEMO participants and identified FGF23 trajectories using group-based modeling. Logistic regression determined predictors of trajectories. Cox regression models evaluated the association between trajectory and all-cause mortality. RESULTS: We identified 5 distinct FGF23 trajectory groups during the initial 24 months: low stable, low increasing, elevated increasing, elevated decreasing, and elevated stable. In multivariable models, diabetes, high dose dialysis, no venous catheter, low serum calcium, phosphorus, and interleukin-6, no vitamin D analog use, and greater residual kidney function were associated with the low stable trajectory group compared to the elevated stable group. High flux dialysis, no venous catheter, and low serum phosphorus and 25-hydroxyvitamin D were associated with the elevated decreasing trajectory group compared to the elevated stable group. After full adjustment, the low stable trajectory group was associated with reduced mortality (hazard ratio [HR] 0.61; 95% CI -0.41-0.91) compared to the elevated stable trajectory group. CONCLUSIONS: We identified 5 distinct FGF23 trajectories over 24 months among HEMO study participants including a decreasing trajectory. The low stable FGF23 trajectory was associated with a reduced HR of all-cause mortality.

One-Year Historical Cohort Study of the Phosphate Binder Sucroferric Oxyhydroxide in Patients on Maintenance Hemodialysis.

OBJECTIVE: The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. DESIGN: Historical cohort analyses of de-identified electronic medical records. SUBJECTS: In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. MAIN OUTCOME MEASURES: Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5 mg/dL) and mean number of PB pills/day. RESULTS: Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P < .0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P < .0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women). CONCLUSION: Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status.

Risk of adverse maternal and fetal outcomes during pregnancy in living kidney donors: A matched cohort study.

BACKGROUND: We examined the risk of adverse pregnancy outcomes in primiparous kidney donors compared to matched controls. METHODS: Fifty-nine women with a history of kidney donation prior to their first pregnancy with normal renal function and no history of kidney disease, diabetes or chronic hypertension were matched 1:4 by age (within 2 years) and race to women with two kidneys using data from an integrated healthcare delivery system. Adverse pregnancy outcomes were defined as preterm delivery (delivery <37 weeks), delivery via cesarean section, gestational hypertension, preeclampsia/eclampsia, gestational diabetes, length of stay in the hospital >3 days, infant death/transfer to acute facility and low birthweight (<2500 g). RESULTS: Living kidney donors did not have a higher risk of adverse outcomes compared to matched controls. There was a trend toward an increased risk of preeclampsia/eclampsia in kidney donors but it did not reach statistical significance (Odds ratio [OR]: 2.96, 95% CI: 0.98-8.94, P = 0.06). However, in kidney donors ≤30 years of age, there was a fourfold increased risk of preeclampsia/eclampsia (OR: 4.09, 95% CI: 1.07-15.59, P = 0.04). CONCLUSION: Overall, the risk of pregnancy-associated complications following kidney donation is small but potential female kidney donors should be counseled on the possible increased risk of preeclampsia.

The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a "controversies conference" on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference. Until newer measurement methods are widely used, the panel agreed that clinicians should classify 25(OH)D "adequacy" as concentrations > 20ng/mL without evidence of counter-regulatory hormone activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D concentrations < 15ng/mL should be treated irrespective of parathyroid hormone level. Patients with 25(OH)D concentrations between 15 and 20ng/mL may not require treatment if there is no evidence of counter-regulatory hormone activity. The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or calcifediol) should be supplemented before giving activated vitamin D compounds. The compounds need further study evaluating important outcomes that observational studies have linked to low 25(OH)D levels, such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. We urge further research funding in this field.

Personalized Management of Bone and Mineral Disorders and Precision Medicine in End-Stage Kidney Disease.

Chronic kidney disease mineral bone disorder (CKD-MBD) is common in end-stage renal disease and is associated with an increased risk of cardiovascular morbidity and mortality. Mainstays of treatment include decreasing serum phosphorus level toward the normal range with dietary interventions and phosphate binders and treating increased parathyroid hormone levels with activated vitamin D and/or calcimimetics. There is significant variation in serum levels of mineral metabolism markers, intestinal absorption of phosphorus, and therapeutic response among individual patients and subgroups of patients with end-stage renal disease. This variation may be partly explained by polymorphisms in genes associated with calcium and phosphorus homeostasis such as the calcium-sensing receptor gene, the vitamin D-binding receptor gene, and genes associated with vascular calcification. In this review, we discuss how personalized medicine may be used for the management of CKD-MBD and how it ultimately may lead to improved clinical outcomes. Although genetic variants may seem attractive targets to tailor CKD-MBD therapy, complete understanding of how these polymorphisms function and their clinical utility and applicability to personalized medicine need to be determined.

Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial.

BACKGROUND AND OBJECTIVES: High circulating vitamin D levels are associated with lower cardiovascular mortality in CKD, possibly by modifying endothelial function. We examined the effect of calcitriol versus cholecalciferol supplementation on vascular endothelial function in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a prospective, double-blind, randomized trial of 128 adult patients with eGFR=15-44 ml/min per 1.73 m2and serum 25-hydroxyvitamin D level <30 ng/ml at the University of Colorado. Participants were randomly assigned to oral cholecalciferol (2000 IU daily) or calcitriol (0.5 µg) daily for 6 months. The primary end point was change in brachial artery flow-mediated dilation. Secondary end points included changes in circulating markers of mineral metabolism and circulating and cellular markers of inflammation. RESULTS: One hundred and fifteen patients completed the study. The mean (SD) age and eGFR of participants were 58±12 years old and 33.0±10.2 ml/min per 1.73 m2, respectively. There were no significant differences between groups at baseline. After 6 months, neither calcitriol nor cholecalciferol treatment resulted in a significant improvement in flow-mediated dilation (mean±SD percentage flow-mediated dilation; calcitriol: baseline 4.8±3.1%, end of study 5.1±3.6%; cholecalciferol: baseline 5.2±5.2%, end of study 4.7±3.6%); 25-hydroxyvitamin D levels increased significantly in the cholecalciferol group compared with the calcitriol group (cholecalciferol: 11.0±9.5 ng/ml; calcitriol: -0.8±4.8 ng/ml; P<0.001). Parathyroid hormone levels decreased significantly in the calcitriol group compared with the cholecalciferol group (median [interquartile range]; calcitriol: -22.1 [-48.7-3.5] pg/ml; cholecalciferol: -0.3 [-22.6-16.9] pg/ml; P=0.004). CONCLUSIONS: Six months of therapy with calcitriol or cholecalciferol did not improve vascular endothelial function or improve inflammation in patients with CKD.

Association of Unilateral Renal Agenesis With Adverse Outcomes in Pregnancy: A Matched Cohort Study.

BACKGROUND: Data regarding the effect of a solitary kidney during pregnancy have come from studies of living kidney donors. We evaluated the risk for adverse pregnancy outcomes in women with a single kidney from renal agenesis. STUDY DESIGN: Matched cohort study. SETTING & PARTICIPANTS: Using data from 7,079 childbirths from an integrated health care delivery system from 1996 through 2015, we identified births from women with renal agenesis. Only first pregnancies and singleton births were included. After excluding those with diabetes and kidney disease, 200 women with renal agenesis were matched 1:4 by age (within 2 years), race, and history of hypertension to women with 2 kidneys. PREDICTOR: Renal agenesis defined by International Classification of Diseases, Ninth Revision (ICD-9) codes prior to pregnancy. OUTCOMES: The primary outcome was adverse maternal outcomes, including preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, and hospital length of stay. Adverse neonatal end points were considered as a secondary outcome and included low birth weight (<2,500g) and infant death/transfer to acute inpatient facility. RESULTS: Mean gestational age at delivery was 37.9±2.1 weeks for women with renal agenesis compared to 38.6±1.8 weeks for women with 2 kidneys. Compared with women with 2 kidneys, those with renal agenesis had increased risk for preterm delivery (OR, 2.88; 95% CI, 1.86-4.45), delivery by cesarean section (OR, 2.11; 95% CI, 1.49-2.99), preeclampsia/eclampsia (OR, 2.41; 95% CI, 1.23-4.72), and length of stay longer than 3 days (OR, 1.81; 95% CI, 1.18-2.78). Renal agenesis was not significantly associated with increased risk for infant death/transfer to acute facility (OR, 2.60; 95% CI, 0.57-11.89) or low birth weight after accounting for preterm delivery (OR, 2.11; 95% CI, 0.76-5.88). LIMITATIONS: Renal agenesis was identified by ICD-9 code, not by imaging of the abdomen. CONCLUSION: Women with unilateral renal agenesis have a higher risk for adverse outcomes in pregnancy.

Kidney disease and maternal and fetal outcomes in pregnancy.

BACKGROUND: Pregnancy in kidney disease is considered high risk, but the degree of this risk is unclear. We tested the hypothesis that kidney disease in pregnancy is associated with adverse maternal and fetal outcomes. STUDY DESIGN: Retrospective study comparing pregnant women with and without kidney disease. SETTING & PARTICIPANTS: Using data from an integrated health care delivery system from 2000 through 2013, a total of 778 women met the criteria for kidney disease. Using a pool of 74,105 women without kidney disease, we selected 778 women to use for matches for the women with kidney disease. These women were matched 1:1 by age, race, and history of diabetes, chronic hypertension, liver disease, and connective tissue disease. PREDICTOR: Kidney disease was defined using the NKF-KDOQI definition for chronic kidney disease or International Classification of Diseases, Ninth Revision codes prior to pregnancy or serum creatinine level > 1.2mg/dL and/or proteinuria in the first trimester. OUTCOMES & MEASUREMENTS: Maternal outcomes included preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, length of stay at hospital (>3 days), and maternal death. Fetal outcomes included low birth weight (weight < 2,500g), small for gestational age, number of admissions to neonatal intensive care unit, and infant death. RESULTS: Compared with women without kidney disease, those with kidney disease had 52% increased odds of preterm delivery (OR, 1.52; 95% CI, 1.16-1.99) and 33% increased odds of delivery by cesarean section (OR, 1.33; 95% CI, 1.06-1.66). Infants born to women with kidney disease had 71% increased odds of admission to the neonatal intensive care unit or infant death compared with infants born to women without kidney disease (OR, 1.71; 95% CI, 1.17-2.51). Kidney disease also was associated with 2-fold increased odds of low birth weight (OR, 2.38; 95% CI, 1.64-3.44). Kidney disease was not associated with increased risk of maternal death. LIMITATIONS: Data for level of kidney function and cause of death not available. CONCLUSIONS: Kidney disease in pregnancy is associated independently with adverse maternal and fetal outcomes when other comorbid conditions are controlled by matching.

Vitamin D level and risk of community-acquired pneumonia and sepsis.

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08-6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11-2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis.

Vascular calcification in chronic kidney disease: role of disordered mineral metabolism.

In patients with chronic kidney disease (CKD), vascular calcification is associated with significant morbidity and mortality. The prevalence of vascular calcification increases as glomerular filtration rate (GFR) declines and calcification occurs years earlier in CKD patients than in the general population. The mechanisms of vascular calcification in CKD patients are complex and not completely understood but likely involve non-traditional risk factors, which may be unique to patients with CKD. These unique risk factors may predispose patients to early and more accelerated calcification. Experimental and clinical studies show that disorders in mineral metabolisms including calcium and phosphorus homeostasis initiate and promote vascular calcification in patients with CKD. It is currently unknown if vascular calcification can be prevented or reversed with therapies aimed at maintaining calcium and phosphorus homeostasis. This review focuses on the potential mechanisms by which disordered mineral metabolism may promote vascular calcification in patients with CKD.

The effect of combined calcium and cholecalciferol supplementation on bone mineral density in elderly women with moderate chronic kidney disease.

AIMS: To examine the effect of combined calcium and vitamin D3 supplementation on bone mineral density (BMD) inpatients with chronic kidney disease (CKD). METHODS: We performed a post-hoc analysis of the DECALYOS II, a 2-year randomized, double-blind, placebo-controlled study of 610 women randomized to: calcium-vitamin D3 fixed combination, calcium plus vitamin D3 separate combination, or placebo. Both active treatment groups received the same daily amount of calcium (1,200 mg) and vitamin D3 (800 IU). BMD of the distal radius was measured by single X-ray absorptiometry at baseline, 12 and 24 months. RESULTS: At baseline 47.2%, 36.4% and 16.4% of the study population had an eGFR ≥ 60, 45 -59, and < 45 ml/min/1.73 m2, respectively. Both active regimens vs. placebo markedly increased serum 25-hydroxyvitamin D levels from baseline in all eGFR groups (p 0.22 for all time points). CONCLUSION: Combined calcium and vitamin D3 supplementation was effective in reducing rate of BMD loss in women with moderate CKD.

The role of phosphorus in the development and progression of vascular calcification.

Vascular calcification is associated with significant cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Factors unique to patients with CKD, such as hyperphosphatemia, predispose these patients to early and progressive vascular calcification. Hyperphosphatemia appears to be involved in a number of mechanisms that trigger and advance the progression of vascular calcification, including (1) transition of vascular smooth muscle cells (VSMCs) from a contractile to an osteochondrogenic phenotype and mineralization of VSMC matrix through sodium-dependent phosphate cotransporters, (2) induction of VSMC apoptosis, (3) inhibition of monocyte/macrophage differentiation into osteoclast-like cells, (4) elevation of fibroblast growth factor 23 levels, and (5) decreases in klotho expression. Whether vascular calcification can be prevented or reversed with strategies aimed at maintaining phosphate homeostasis presently is unknown. This review discusses these mechanisms in depth, exploring the interplay among vascular calcification promoters, inhibitors, and substrate that affect phosphorus handling leading to vascular calcification in individuals with CKD.

Relation of serum phosphorus levels to ankle brachial pressure index (from the Third National Health and Nutrition Examination Survey).

Higher levels of serum phosphorus that remain within the reference range are associated with increased risk of cardiovascular disease (CVD). However, the mechanisms by which higher serum phosphorus concentrations may contribute to the development of CVD remain unclear. Cross-sectional association between serum phosphorus levels and arterial stiffness as estimated by an ankle brachial pressure index (ABPI) >1.3 was examined in 581 participants in the Third National Health and Nutrition Examination Survey. Logistic regression analysis was performed to evaluate whether higher serum phosphorus levels were associated with high ABPI, independently of several potential confounders. Of 581 participants, 38% and 10% had a serum phosphorus levels >3.5 and >4.0 mg/dl, respectively. An ABPI >1.3 was present in 7.3% of participants. Higher quartiles of serum phosphorus levels were associated with a greater prevalence of high ABPI: 5.4%, 3.7%, 7.8%, and 12.9% for quartiles 1 (<3.1 mg/dl), 2 (3.1 to 3.4 mg/dl), 3 (3.4 to 3.7 mg/dl), and 4 (3.7 to 5.0 mg/dl), respectively. There was a strong, positive association between the highest quartile of serum phosphorus (3.7 to 5.0 mg/dl) and high ABPI compared to the reference group (3.1 to 3.4 mg/dl) after adjustment for demographics, traditional CVD risk factors, kidney function, C-reactive protein, serum calcium, and 25-hydroxyvitamin D levels (adjusted odds ratio 4.78, 95% confidence interval 1.73 to 13.2, p = 0.003). In conclusion, serum phosphorus levels, even within the reference range, are independently associated with high ABPI, a marker of arterial stiffness, in the US adult population.

The effect of combined calcium and vitamin D3 supplementation on serum intact parathyroid hormone in moderate CKD.

BACKGROUND: Studies addressing the effects of vitamin D(3) supplementation on secondary hyperparathyroidism in patients with moderate chronic kidney disease are scarce. STUDY DESIGN: Post hoc analysis of the randomized clinical trial Vitamin D, Calcium, Lyon Study II (DECALYOS II) to assess effects according to baseline estimated glomerular filtration rate (eGFR). SETTING & PARTICIPANTS: Multicenter, randomized, double-blinded, placebo-controlled study of 639 elderly women randomly assigned to calcium-vitamin D(3) fixed combination; calcium plus vitamin D(3) separate combination, or placebo. INTERVENTIONS: Placebo or calcium (1,200 mg) and vitamin D(3) (800 IU) in fixed or separate combination. OUTCOMES & MEASUREMENTS: Proportion of participants with a mean decrease in intact parathyroid hormone (iPTH) level of 30% or greater. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and categorized as 60 or greater, 45 to 59, and less than 45 mL/min/1.73 m(2). RESULTS: 610 participants had an eGFR at baseline: 288 (47.2%), 222 (36.4%), and 100 (16.4%) were in each decreasing eGFR category. Across decreasing eGFR groups, 88%, 86%, and 89% had 25-hydroxyvitamin D (25[OH]D) levels less than 15 ng/mL at baseline. On treatment, similar improvements in the proportion of participants achieving 25(OH)D levels greater than 30 ng/mL at 6 months were seen in all kidney function groups (43%, 49%, and 41%, respectively). Active regimens versus placebo increased mean 25(OH)D levels from baseline in all eGFR groups at all times (P < 0.001 for all). The proportion with a 30% or greater decrease in iPTH level at 6 months was 50% in all eGFR groups on treatment versus 6% to 9% for placebo (P < 0.001 for all). The effects of the intervention on iPTH levels did not differ according to baseline eGFR (interaction P > 0.1 for all times). LIMITATIONS: This study included only elderly white women. CONCLUSION: Vitamin D(3) was effective in increasing 25(OH)D and decreasing iPTH levels in patients with moderate chronic kidney disease.

Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) have a reduced lifespan, and a substantial proportion of these individuals die from cardiovascular disease. Although a large percentage of patients with CKD have traditional cardiac risk factors such as diabetes, hypertension and abnormalities in cholesterol, interventions to address these factors--which have significantly decreased cardiovascular mortality in the general population--have not shown such benefit in the CKD population. In addition, the severity and extent of cardiovascular complications in patients with CKD is disproportionate to the number and severity of traditional risk factors. This realization has focused attention on nontraditional cardiac risk factors that are particularly relevant to patients with CKD, including decreased hemoglobin levels, microalbuminuria, increased inflammation and oxidative stress, and abnormalities in bone and mineral metabolism. However, large prospective trials in patients with advanced CKD or in those requiring chronic dialysis have not shown that normalization of these nontraditional risk factors improves survival. Moreover, the mechanisms by which these nontraditional risk factors contribute to cardiovascular disease are unknown. Therefore, although current treatment of patients with CKD includes management of traditional and nontraditional risk factors, the value of modifying some nontraditional risk factors remains unclear.