Effect of Lanthanum Carbonate on Serum Phosphate, Oxidative Stress, and Vascular Dysfunction in Chronic Kidney Disease.

BACKGROUND: Vascular endothelial dysfunction and arterial stiffness are common in chronic kidney disease (CKD) and independently predict cardiovascular disease (CVD). Elevated serum phosphorus, even within the normal range, associates with CVD and mortality in CKD. Excess phosphorus may increase oxidative stress leading to vascular dysfunction. METHODS: Randomized double-blind trial in which we compared lanthanum carbonate, a non-calcium phosphate binder, with placebo on vascular function and endothelial and circulating measures of oxidative stress and inflammation in 54 participants with CKD 3b-4 and normal phosphorus levels. The primary endpoints were change in brachial artery flow-mediated dilation (FMDBA) and carotid-to-femoral pulse-wave velocity (cfPWV) at 12 weeks. Mechanistic endpoints were changes from baseline in FMDBA after ascorbic acid infusion and circulating and endothelial markers of oxidative stress and inflammation. RESULTS: Age was 65±8 years and eGFR 38±14 mL/min/1.73m2. At 12 weeks serum phosphorus did not change with lanthanum (3.44±0.47 mg/dL vs. 3.44±0.52 mg/dL; p=0.94) but tended to increase with placebo (3.42±0.80 mg/dL vs. 3.74±1.26 mg/dL; p=0.09). FMDBA and cfPWV did not change from baseline in either group. FMDBA lanthanum 3.13%±2.87% to 2.73%±2.48% vs. placebo 3.74%±2.86% to 3.09%±2.49%; p=0.67. cfPWV lanthanum 1214±394 cm/sec to 1216±322 cm/sec vs. placebo 993±289 cm/sec to 977±254 cm/sec; p=0.77. Ascorbic acid infusion to inhibit oxidative stress did not differentially affect FMDBA. Circulating and endothelial markers of oxidative stress and inflammation did not differ between groups. CONCLUSIONS: Lanthanum carbonate did not discernibly affect vascular endothelial function, arterial stiffness, or markers of endothelial oxidative stress among participants with CKD 3b-4 and normophosphatemia.

Statin therapy in patients with early-stage autosomal dominant polycystic kidney disease: Design and baseline characteristics.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and continued growth of multiple cysts in the kidneys leading to ultimate loss of kidney function in most patients. Currently, tolvaptan is the only agency approved therapy to slow kidney disease advancement in patients with faster progressing disease underscoring the need for additional ADPKD therapies suitable for all patients. We previously showed that pravastatin slowed kidney disease progression in children and young adults with ADPKD. However, the intervention has not been tested in an adult cohort. AIMS: The aim of the study is to conduct a single center, randomized, placebo-controlled double-blinded clinical trial to determine the efficacy of pravastatin on slowing kidney disease progression in adult patients with early stage ADPKD. METHODS: One hundred and fifty adult patients with ADPKD and eGFR ≥60 ml/min/1.73m2 will be enrolled in the study and randomized to receive 40 mg/day pravastatin or placebo for a period of 2-years. OUTCOMES: The primary outcome of the trial is change in total kidney volume assessed by magnetic resonance imaging (MRI). Secondary outcomes include change in kidney function by iothalamate GFR and renal blood flow and markers of inflammation and oxidative stress. CONCLUSION: This study will assess the kidney therapeutic benefits of pravastatin in adult patients with ADPKD. The recruitment goal of 150 subjects was attained and the study is ongoing. REGISTRATION: This study is registered on Clinicaltrials.gov # NCT03273413.

Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis.

Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association of sex hormone levels with the risk of CVD events and mortality (CVD and all-cause) in the CKD population. Articles were systematically searched in CINAHL, Cochrane, and PubMed. A total of 1739 articles were independently screened by two reviewers and 17 prospective cohort studies were included. The clinical conditions of the patients were those with non-dialysis CKD [mean/median estimated glomerular filtration rate (eGFR) between 15-51 ml/min/1.73 m2 ] and those on chronic dialysis (mean/median vintage between 6-125 months). The sample size ranged from 111 to 2419 and the mean/median age of subjects ranged from 52 to 72 years. The sex hormones studied were testosterone, estradiol, prolactin, dehydroepiandrosterone sulfate, and relaxin. A random-effects model was used to generate a pooled hazard ratio (HR) to evaluate the association of total testosterone levels with the risk of CVD and all-cause mortality. Most studies examined total testosterone levels (11 out of 17 studies) and studied only male patients (12 out of 17 studies). A lower total testosterone level was associated with a higher risk of CVD mortality [HR 4.37 (95% CI 1.40-13.65)] and all-cause mortality [1.96 (1.35-2.83)] in males with CKD. To conclude, there is a strong need for additional studies examining the association of sex hormones with cardiovascular and mortality risk in female patients with CKD.

Association of Monocyte Count and Monocyte/Lymphocyte Ratio with the Risk of Cardiovascular Outcomes in Patients with CKD.

Background: Emerging evidence suggests an association of higher monocyte count and monocyte/lymphocyte ratio (MLR) with the risk of cardiovascular disease (CVD) in individuals without chronic kidney disease (CKD); however, limited studies have examined if this association translates to the CKD population. This study examined whether monocyte count and MLR are associated with the risk of CVD, CVD death, and all-cause death in patients with nondialysis CKD who participated in the Chronic Renal Insufficiency Cohort observational study. Methods: Baseline monocyte count and MLR were categorized into tertiles and also modeled continuously. Cox proportional hazards models were used to examine the association between monocyte count (primary predictor) and MLR (secondary predictor) at baseline and time to a composite of CVD events, including heart failure, myocardial infarction, ischemic stroke, and peripheral artery disease (primary outcome). Secondary outcomes were time to CVD death and all-cause death. Results: The median follow-up time was 9 years for CVD events and 11.7 years for death. In the fully adjusted model, participants with a higher monocyte count and MLR had a greater risk of CVD events (hazard ratio [HR] per doubling of monocyte count=1.2 [95% CI, 1.1 to 1.31]; HR per doubling of MLR=1.26 [95% CI, 1.16 to 1.36]), CVD death (HR=1.18 [95% CI, 0.99 to 1.41]; HR=1.27 [95% CI, 1.1 to 1.48]), and all-cause death (HR=1.17 [95% CI, 1.06 to 1.3]; HR=1.18 [95% CI, 1.09 to 1.29]). Conclusions: These results suggest that monocyte count and MLR may have the potential to be cost-effective, clinically available indicators of CVD risk in the CKD population.

Deoxycholic Acid and Coronary Artery Calcification in the Chronic Renal Insufficiency Cohort.

Background Deoxycholic acid (DCA) is a secondary bile acid that may promote vascular calcification in experimental settings. Higher DCA levels were associated with prevalent coronary artery calcification (CAC) in a small group of individuals with advanced chronic kidney disease. Whether DCA levels are associated with CAC prevalence, incidence, and progression in a large and diverse population of individuals with chronic kidney disease stages 2 to 4 is unknown. Methods and Results In the CRIC (Chronic Renal Insufficiency Cohort) study, we evaluated cross-sectional (n=1057) and longitudinal (n=672) associations between fasting serum DCA levels and computed tomographic CAC using multivariable-adjusted regression models. The mean age was 57±12 years, 47% were women, and 41% were Black. At baseline, 64% had CAC (CAC score >0 Agatston units). In cross-sectional analyses, models adjusted for demographics and clinical factors showed no association between DCA levels and CAC >0 compared with no CAC (prevalence ratio per 1-SD higher log DCA, 1.08 [95% CI, 0.91-1.26). DCA was not associated with incident CAC (incidence per 1-SD greater log DCA, 1.08 [95% CI, 0.85-1.39]) or CAC progression (risk for increase in ≥100 and ≥200 Agatston units per year per 1-SD greater log DCA, 1.05 [95% CI, 0.84-1.31] and 1.26 [95% CI, 0.77-2.06], respectively). Conclusions Among CRIC study participants, DCA was not associated with prevalent, incident, or progression of CAC.

Deoxycholic Acid and Risks of Cardiovascular Events, ESKD, and Mortality in CKD: The CRIC Study.

RATIONALE & OBJECTIVE: Elevated levels of deoxycholic acid (DCA) are associated with adverse outcomes and may contribute to vascular calcification in patients with chronic kidney disease (CKD). We tested the hypothesis that elevated levels of DCA were associated with increased risks of cardiovascular disease, CKD progression, and death in patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We included 3,147 Chronic Renal Insufficiency Cohort study participants who had fasting DCA levels. The average age was 59 ± 11 years, 45.3% were women, 40.6% were African American, and the mean estimated glomerular filtration rate was 42.5 ± 16.0 mL/min/1.73 m2. PREDICTOR: Fasting DCA levels in Chronic Renal Insufficiency Cohort study participants. OUTCOMES: Risks of atherosclerotic and heart failure events, end-stage kidney disease (ESKD), and all-cause mortality. ANALYTICAL APPROACH: We used Tobit regression to identify predictors of DCA levels. We used Cox regression to examine the association between fasting DCA levels and clinical outcomes. RESULTS: The strongest predictors of elevated DCA levels in adjusted models were increased age and nonuse of statins. The associations between log-transformed DCA levels and clinical outcomes were nonlinear. After adjustment, DCA levels above the median were independently associated with higher risks of ESKD (HR, 2.67; 95% CI, 1.51-4.74) and all-cause mortality (HR, 2.13; 95% CI, 1.25-3.64). DCA levels above the median were not associated with atherosclerotic and heart failure events, and DCA levels below the median were not associated with clinical outcomes. LIMITATIONS: We were unable to measure DCA longitudinally or in urinary or fecal samples, and we were unable to measure other bile acids. We also could not measure many factors that affect DCA levels. CONCLUSIONS: In 3,147 participants with CKD stages 2-4, DCA levels above the median were independently associated with ESKD and all-cause mortality.

Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a randomized, placebo-controlled, double-blind trial, 68 children/young adults 6-25 years of age with ADPKD and eGFR>80 ml/min per 1.73 m2 were randomized to either curcumin supplementation (25 mg/kg body weight per day) or placebo administered in powder form for 12 months. The coprimary outcomes were brachial artery flow-mediated dilation and aortic pulse-wave velocity. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume) by magnetic resonance imaging. In a subgroup of participants ≥18 years, vascular oxidative stress was measured as the change in brachial artery flow-mediated dilation following an acute infusion of ascorbic acid. RESULTS: Enrolled participants were 18±5 (mean ± SD) years, 54% were girls, baseline brachial artery flow-mediated dilation was 9.3±4.1% change, and baseline aortic pulse-wave velocity was 512±94 cm/s. Fifty-seven participants completed the trial. Neither coprimary end point changed with curcumin (estimated change [95% confidence interval] for brachial artery flow-mediated dilation [percentage change]: curcumin: 1.14; 95% confidence interval, -0.84 to 3.13; placebo: 0.33; 95% confidence interval, -1.34 to 2.00; estimated difference for change: 0.81; 95% confidence interval, -1.21 to 2.84; P=0.48; aortic pulse-wave velocity [centimeters per second]: curcumin: 0.6; 95% confidence interval, -25.7 to 26.9; placebo: 6.5; 95% confidence interval, -20.4 to 33.5; estimated difference for change: -5.9; 95% confidence interval, -35.8 to 24.0; P=0.67; intent to treat). There was no curcumin-specific reduction in vascular oxidative stress or changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared with placebo. CONCLUSIONS: Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD, NCT02494141. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN08950621.mp3.

Lower serum bicarbonate is associated with an increased risk of acute kidney injury.

BACKGROUND: Lower serum bicarbonate levels are associated with an increased risk of kidney disease progression. Whether lower serum bicarbonate levels are associated with an increased risk of developing acute kidney injury (AKI) is unclear. METHODS: We included 8393 patients from the Systolic Blood Pressure Intervention Trial (SPRINT) that had baseline serum bicarbonate levels and complete data available. AKI was a predetermined adjudicated adverse event that was determined by hospital admission and discharge records with AKI as a recorded diagnosis. Serum bicarbonate was examined in clinically significant cutoffs ≤ 24, 25-28 and > 28 mEq/L, with 25-28 mEq/L as the reference group. Cox proportional hazard models were used to examine the association between serum bicarbonate and development of AKI. RESULTS: The mean (SD) age, estimated glomerular filtration rate (eGFR), and serum bicarbonate level at baseline were 68 (9) years, 77 (23) ml/min/1.73m2 and 26.3 (2.6) mEq/L, respectively. Participants with serum bicarbonate levels ≤ 24 mEq/L were more likely to be male and to have lower baseline eGFR. After a median follow-up time of 3.3 years, 293 participants developed AKI. More patients in the lower bicarbonate group developed AKI (6.1% vs 2.8% in the 25-28 mEq/L and 2.1% in the > 28 mEq/L). A bicarbonate level ≤ 24 mEq/L was associated with a significantly increased risk of AKI compared to those with a bicarbonate level of 25-28 mEq/L after full adjustment (HR 1.42, 95% CI 1.1-1.8). CONCLUSION: Lower serum bicarbonate levels are an independent risk factor for the development of AKI.

FGF23, Frailty, and Falls in SPRINT.

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is associated with frailty. Fibroblast growth factor 23 (FGF23) is elevated in CKD and associated with frailty among non-CKD older adults and individuals with human immunodeficiency virus. Whether FGF23 is associated with frailty and falls in CKD is unknown. DESIGN: Cross-sectional and longitudinal observational study. SETTING: Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial evaluating standard (systolic blood pressure [SBP] <140 mm Hg) versus intensive (SBP <120 mm Hg) blood pressure lowering on cardiovascular and cognitive outcomes among older adults without diabetes mellitus. PARTICIPANTS: A total of 2,376 participants with CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 ). MEASUREMENTS: The exposure variable was intact FGF23. We used multinomial logistic regression to determine the cross-sectional association of intact FGF23 with frailty and Cox proportional hazards analysis to determine the longitudinal association with incident falls. Models were adjusted for demographics, comorbidities, randomization group, antihypertensives, eGFR, mineral metabolism markers, and frailty. RESULTS: After adjustment, the odds ratio for prevalent frailty versus non-frailty per twofold higher FGF23 was 1.34 (95% confidence interval [CI] = 1.01-1.77). FGF23 levels in the highest quartile versus the lowest quartile demonstrated more than a twofold increased fall risk (hazard ratio [HR] = 2.32; 95% CI = 1.26-4.26), and the HR per twofold higher FGF23 was 1.99 (95% CI = 1.48-2.68). CONCLUSION: Among SPRINT participants with CKD, FGF23 was associated with prevalent frailty and falls.

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.

BACKGROUND: Increased arterial stiffness and vascular endothelial dysfunction are important nontraditional cardiovascular risk factors evident in patients with CKD. Vascular oxidative stress and inflammation may contribute to vascular dysfunction in CKD, but direct evidence is lacking. METHODS: We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with moderate-to-severe CKD (eGFR 15-59 ml/min per 1.73 m2) and in healthy controls. Change in brachial artery flow-mediated dilation after an acute infusion of ascorbic acid to inhibit vascular oxidative stress (versus saline) was also measured. Protein expression of vascular endothelial cells collected from a peripheral vein and ELISAs to assess circulating markers were also performed. RESULTS: A total of 64 participants with CKD (mean±SD, 65±8 years) and 17 healthy controls (60±5 years) were included. Carotid-femoral pulse-wave velocity was greater in participants with CKD compared with healthy controls (1071±336 versus 732±128 cm/s; P<0.001). Brachial artery flow-mediated dilation was lower in participants with CKD compared with healthy controls (3.5%±2.8% versus 5.5%±3.2%; P=0.02). Circulating inflammation markers (C-reactive protein and IL-6) were elevated in the CKD group (P≤0.02). Endothelial cell protein expression of NADPH (intensity versus human umbilical vein endothelial cell control, 1.48±0.28 versus 1.25±0.31; P=0.05) was greater in participants with CKD. However, ascorbic acid significantly improved brachial artery flow-mediated dilation in control participants (saline, 5.5±3.2; ascorbic acid, 6.8±3.6); as compared with participants with CKD (saline, 3.5±2.8; ascorbic acid, 3.6±3.2) (group×condition interaction P=0.04), suggesting vascular oxidative stress could not be overcome with ascorbic acid in participants with CKD. CONCLUSIONS: Vascular oxidative stress is present in CKD, which cannot be overcome with acute infusion of ascorbic acid.

Curcumin therapy to treat vascular dysfunction in children and young adults with autosomal dominant polycystic kidney disease: Design and baseline characteristics of participants.

Although often considered to be a disease of adults, complications of autosomal dominant polycystic kidney disease (ADPKD) begin in childhood. While the hallmark of ADPKD is the development and continued growth of multiple renal cysts that ultimately result in loss of kidney function, cardiovascular complications are the leading cause of death among affected patients. Vascular dysfunction (endothelial dysfunction and large elastic artery stiffness) is evident very early in the course of the disease and appears to involve increased oxidative stress and inflammation. Treatment options to prevent cardiovascular disease in adults with ADPKD are limited, thus childhood may represent a key therapeutic window. Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric. This spice has a unique ability to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation. Here we describe our ongoing randomized, placebo-controlled, double-blind clinical trial to assess the effect of curcumin therapy on vascular function and kidney growth in 68 children and young adults age 6-25 years with ADPKD. Baseline demographic, vascular, and kidney volume data are provided. This study has the potential to establish a novel, safe, and facile therapy for the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of children and young adults with ADPKD.

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial
.

AIMS: Arterial stiffness increases with both advancing age and chronic kidney disease (CKD) and may contribute to kidney function decline, but evidence is inconsistent. We hypothesized that greater baseline arterial stiffness (assessed as pulse pressure (PP) and carotid-femoral pulse-wave velocity CFPWV)) was independently associated with kidney disease progression over the follow-up period (3.8 years) in the Systolic Blood Pressure Intervention Trial (SPRINT). MATERIALS AND METHODS: 8,815 SPRINT participants were included in the analysis of PP. 592 adults who participated in a SPRINT ancillary study that measured CFPWV were included in subgroup analyses. Cox proportional hazards analysis was used to examine the association between PP and time to kidney disease progression endpoints: (A) incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 in non-CKD participants at baseline; (B) 50% decline in eGFR, initiation of dialysis, or transplant in those with baseline CKD. Mixed model analyses examined the association of baseline PP/CFPWV with follow-up eGFR. RESULTS AND CONCLUSION: Mean ± SD age was 68 ± 10 years, baseline PP was 62 ± 14 mmHg, and CFPWV was 10.8 ± 2.7 m/s. In the fully adjusted model, PP ≥ median was associated with an increased hazard of kidney disease progression endpoints (HR: 1.93 (1.43 - 2.61)). The association remained significant in individuals without (2.05 (1.47 - 2.87)) but not with baseline CKD (1.28 (0.55 - 2.65)). In fully adjusted models, higher baseline PP associated with eGFR decline (p < 0.0001 (all, CKD, non-CKD)), but baseline CFPWV did not. Among older adults at high risk for cardiovascular events, baseline PP was associated with kidney disease progression.

Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins and Inflammation in CKD.

BACKGROUND: Recent evidence suggests the systemic accumulation of by-products of gut microbes contributes to cardiovascular morbidity in patients with CKD. Limiting the generation of toxic bacterial by-products by manipulating the intestinal microbiota may be a novel strategy for reducing cardiovascular disease in CKD. Rifaximin is a minimally absorbed, oral antibiotic that targets intestinal pathogens and is commonly used as chronic therapy for the prevention of encephalopathy in patients with cirrhosis. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial to determine the effect of a 10-day course of oral rifaximin 550 mg BID versus placebo on circulating concentrations of gut-derived cardiovascular toxins and proinflammatory cytokines in patients with stage 3-5 CKD (n=38). The primary clinical outcome was change in serum trimethylamine N-oxide (TMAO) concentrations from baseline to study end. Secondary outcomes included change in serum concentrations of p-cresol sulfate, indoxyl sulfate, kynurenic acid, deoxycholic acid, and inflammatory cytokines (C-reactive protein, IL-6, IL-1ß), and change in composition and diversity of fecal microbiota. RESULTS: A total of 19 patients were randomized to each of the rifaximin and placebo arms, with n=17 and n=14 completing both study visits in these respective groups. We observed no difference in serum TMAO change (post-therapy minus baseline TMAO) between the rifaximin and placebo groups (mean TMAO change -3.9±15.4 for rifaximin versus 0.5±9.5 for placebo, P=0.49). Similarly, we found no significant change in serum concentrations for p-cresol sulfate, indoxyl sulfate, kynurenic acid, deoxycholic acid, and inflammatory cytokines. We did observe differences in colonic bacterial communities, with the rifaximin group exhibiting significant decreases in bacterial richness (Chao1, P=0.02) and diversity (Shannon H, P=0.05), along with altered abundance of several bacterial genera. CONCLUSIONS: Short-term rifaximin treatment failed to reduce gut-derived cardiovascular toxins and inflammatory cytokines in patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Rifaximin Therapy in Chronic Kidney Disease, NCT02342639.

Thrombocytopenia After Cardiopulmonary Bypass Is Associated With Increased Morbidity and Mortality.

BACKGROUND: Thrombocytopenia is a risk factor for morbidity and mortality in critically ill patients, and is common after cardiopulmonary bypass (CPB). In this study, we evaluate whether thrombocytopenia after CPB is an independent risk factor for postoperative morbidity and mortality. METHODS: We retrospectively evaluated 1364 patients requiring CPB at the University of Colorado Hospital between January 2011 and May 2016. Platelet nadir, absolute change in platelets, and percent change in platelets were modeled as continuous variables. Patients with postoperative thrombocytopenia (defined a nadir <75 × 103/µL within 72 hours) were also compared with patients without thrombocytopenia in a propensity-matched model. The primary outcome was in-hospital mortality, and secondary outcomes included postoperative infection, postoperative acute kidney injury (AKI), postoperative stroke, and prolonged intensive care unit (ICU) and hospital lengths of stay (LOS). RESULTS: Postoperative thrombocytopenia occurred in 356 (26.0%) patients. In multivariable analysis, platelet nadir was significantly inversely associated with mortality (odds ratio [OR], 0.955; 95% confidence interval [CI], 0.934-0.975; P < .001), postoperative infection (OR, 0.992; 95% CI, 0.986-0.999; P = .03), AKI (all stage) (OR, 0.993; 95% CI, 0.988-0.998; P = .01), AKI (stage 3) (OR, 0.966; 95% CI, 0.951-0.982; P < .001), postoperative stroke (OR, 0.974; 95% CI, 0.956-0.992; P = .006), prolonged ICU stay (OR, 0.986; 95% CI, 0.981-0.991; P < .001), and hospital LOS (OR, 0.998; 95% CI, 0.997-0.999; P = .001). Percent change in platelets from baseline was also significantly associated with all primary and secondary outcomes. CONCLUSIONS: Postoperative thrombocytopenia is independently associated with postoperative mortality, AKI, infection, stroke, and prolonged ICU and hospital LOS. Serial platelet monitoring may help identify patients at higher risk of postoperative complications. Further studies investigating strategies to reduce postoperative thrombocytopenia, including reducing CPB time, are needed.

Mineral Bone Abnormalities and Vascular Calcifications.

Vascular calcification (VC) is common in chronic kidney disease, increases in prevalence as patients progress to end-stage renal disease, and is significantly associated with mortality. VC is a complex and highly regulated process similar to bone formation whereby hydroxyapatite crystals deposit in the intimal or medial layer of arteries. Mineral bone abnormalities are common in chronic kidney disease; reduction in glomerular filtration rate and changes in vitamin D, parathyroid hormone, and fibroblast growth factor 23 result in the dysregulation of phosphorus and calcium metabolism. Cell culture studies, animal models, and observational and clinical studies all suggest this abnormal mineral metabolism plays a role in the initiation and progression of VC in kidney disease. This review will focus on these mineral bone abnormalities and how they may contribute to mechanisms that induce VC in kidney disease.

Incident infection following acute kidney injury with recovery to baseline creatinine: A propensity score matched analysis.

BACKGROUND: Severe acute kidney injury (AKI) is associated with subsequent infection. Whether AKI followed by a return to baseline creatinine is associated with incident infection is unknown. OBJECTIVE: We hypothesized that risk of both short and long term infection would be higher among patients with AKI and return to baseline creatinine than in propensity score matched peers without AKI in the year following a non-infectious hospital admission. DESIGN: Retrospective, propensity score matched cohort study. PARTICIPANTS: We identified 494 patients who were hospitalized between January 1, 1999 and December 31, 2009 and had AKI followed by return to baseline creatinine. These were propensity score matched to controls without AKI. MAIN MEASURES: The predictor variable was AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and by the Kidney Disease Improving Global Outcomes definition, with return to baseline creatinine defined as a decrease in serum creatinine level to within 10% of the baseline value within 7 days of hospital discharge. The outcome variable was incident infection defined by ICD-9 code within 1 year of hospital discharge. RESULTS: AKI followed by return to baseline creatinine was associated with a 4.5-fold increased odds ratio for infection (odds ratio 4.53 [95% CI, 2.43-8.45]; p<0.0001) within 30 days following discharge. The association between AKI and subsequent infection remained significant at 31-60 days and 91 to 365 days but not during 61-90 days following discharge. CONCLUSION: Among patients from an integrated health care delivery system, non-infectious AKI followed by return to baseline creatinine was associated with an increased odds ratio for infection in the year following discharge.