Anna Jovanovich

Association of Complete Recovery From Acute Kidney Injury With Incident CKD Stage 3 and All-Cause Mortality

BACKGROUND There is a gap of knowledge in the long-term outcomes of patients who have complete recovery of kidney function after an episode of acute kidney injury (AKI). We sought to determine whether complete recovery of kidney function after an episode of AKI is associated with the development of incident stage 3 chronic kidney disease (CKD) and mortality in patients with normal baseline kidney function. DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 3,809 patients from an integrated health care delivery system who had a hospitalization between January 1, 1999, and December 31, 2009, with follow-up through March 31, 2010. PREDICTOR AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and using the AKI Network (AKIN) definition, with complete recovery defined as a decrease in serum creatinine level to less than 1.10 times the baseline value. OUTCOMES AND MEASUREMENTS Incident stage 3 CKD persistent for 3 months and all-cause mortality. RESULTS After a median follow-up of 2.5 years, incident stage 3 CKD occurred in 15% and 3% of those with and without AKI, respectively, with an unadjusted HR of 5.93 (95% CI, 4.49-7.84) and HR of 3.82 (95% CI, 2.81-5.19) in propensity score-stratified analyses. Deaths occurred in 35% and 24% of those with and without AKI, respectively, with an unadjusted HR of 1.46 (95% CI, 1.27-1.68). In propensity score-stratified analyses, HR decreased to 1.08 (95% CI, 0.93-1.27). LIMITATIONS Measurements of albuminuria were not available. CONCLUSIONS Complete recovery of kidney function after an episode of AKI in patients with normal baseline kidney function is associated with increased risk of the development of incident stage 3 CKD, but not all-cause mortality.

Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults

OBJECTIVES In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain. METHODS C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH. RESULTS Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95% CI 4.35-9.01] g per doubling of FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95% CI 5.86-13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20-1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97-1.48]). CONCLUSION In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.

Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease

BACKGROUND AND AIMS We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S. METHODS AND RESULTS Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L [30 ± 7 vs. 34 ± 8 ng/mL], P<0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37-75 nmol/L [15-30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90-6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27-5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064-0.96, P=0.02). CONCLUSION Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.

Racial Differences in Markers of Mineral Metabolism in Advanced Chronic Kidney Disease

BACKGROUND AND OBJECTIVES This study examined differences in the concentration of markers of mineral metabolism across race in patients with advanced CKD not requiring dialysis and ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Concentrations of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF-23) were measured in stored plasma samples of 1497 patients with advanced CKD not yet on dialysis and ESRD who participated in the Homocysteine in Kidney and End Stage Renal Disease study. Linear regression models were used to examine the relationship between race and 25(OH)D, 1,25(OH)(2)D, iPTH, and FGF-23 concentrations. RESULTS Non-Hispanic white patients comprised 58% of the cohort, whereas non-Hispanic blacks comprised 42%. Median (interquartile range) FGF-23 concentrations were lower in blacks compared with whites with CKD (323 [181-655] versus 431 [232-1026] RU/ml; P<0.001) but not in ESRD. In adjusted linear regression models, blacks with CKD not requiring dialysis had significantly lower plasma FGF-23 concentrations (difference, -159; 95% confidence interval, -205 to -106; P<0.001) compared with whites, independent of plasma 25(OH)D, 1,25(OH)(2)D, and iPTH concentrations. This difference was not observed in the ESRD group. The magnitude of correlation for the relationships between 1,25(OH)(2)D with iPTH, FGF-23 with 1,25(OH)(2)D, and FGF-23 with iPTH were stronger among blacks than whites with CKD not requiring dialysis. CONCLUSIONS In advanced CKD not requiring dialysis, blacks have lower FGF-23 concentrations than whites. Blacks with CKD and ESRD have lower 25(OH)D and higher iPTH compared with whites, independent of FGF-23 concentrations.

Fibroblast Growth Factor 23, Bone Mineral Density, and Risk of Hip Fracture Among Older Adults: The Cardiovascular Health Study

CONTEXT Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis. OBJECTIVE Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults. DESIGN AND SETTING Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease. PARTICIPANTS Participants included 2008 women and 1329 men ≥65 years from the 1996 to 1997 Cardiovascular Health Study visit. MAIN OUTCOME MEASURES Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants. RESULTS Women had higher plasma FGF23 concentrations than men (75 [56-107] vs 66 [interquartile range = 52-92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95% confidence interval [CI] = 0.001-0.04 g/cm(2), and 0.03 with 95% CI = 0.01-0.06 g/cm(2)). During 9.6 ± 5.1-11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95% CI = 0.78-1.15, and 1.09 with 95% CI = 0.82-1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions). CONCLUSIONS In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk.

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.

25-vitamin D, 1,25-vitamin D, parathyroid hormone, fibroblast growth factor-23 and cognitive function in men with advanced CKD: a veteran population.

Abstract. Cognitive impairment is common in advanced chronic kidney disease (CKD), but little is known about its relation with abnormalities in mineral metabolism. Methods: The longitudinal association between plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF-23) levels and cognitive function was assessed in 605 patients (67 ± 12 years) with advanced CKD not requiring dialysis (n = 247) or end-stage renal disease (ESRD; n = 358) who participated in the Homocysteine Study Cognitive Function Substudy (HOSTCOG)). Cognitive function was assessed using the Telephone Interview for Cognitive Status-modified (TICSm; mean follow-up 3.1 years) and associated with baseline mineral metabolite levels using linear regression analyses. Results: In unadjusted analyses, increasing log 1,25(OH)2D and decreasing log iPTH and FGF-23 levels were associated with worse cognitive status (p < 0.05). In fully adjusted multivariate analyses, the associations were no longer significant. Log 25(OH)D levels were not associated with cognitive function in unadjusted or adjusted analyses. Results were similar when analyzed by tertile or separately within CKD and ESRD groups. Conclusions: These results suggest that mineral metabolism dysregulation does not mediate the impairment in cognitive function common in advanced CKD.

Calcific Uremic Arteriolopathy Revisited

Calciphylaxis was first described in the early 1960s by dermatologist Hans Selye et al. [1][1] as local cutaneous calcification leading to inflammation and skin sclerosis, which is provoked by a mechanical or chemical “challenger” after sensitization with a “systemic calcifying factor.” In

Mineral Metabolites, Angiotensin II Inhibition and Outcomes in Advanced Chronic Kidney Disease

Background: Evidence suggests that the renin-angiotensin-aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD). Methods: In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 ± 6 ml/min/1.73 m2 and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox regression models adjusted for mineral metabolism markers. Results: Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction >0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction <0.001). Conclusions: RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association.

Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices

Background: Dietary sodium may influence cognitive function through its effects on cerebrovascular function and cerebral blood flow. Methods: The aim of this study was to evaluate the association of dietary sodium intake with cognitive decline in community-dwelling older adults. We also evaluated the associations of dietary potassium and sodium:potassium intake with cognitive decline, and associations of these nutrients with micro- and macro-structural brain magnetic resonance imaging (MRI) indices. In all, 1,194 participants in the Health Aging and Body Composition study with measurements of dietary sodium intake (food frequency questionnaire [FFQ]) and change in the modified Mini Mental State Exam (3MS) were included. Results: The age of participants was 74 ± 3 years with a mean dietary sodium intake of 2,677 ± 1,060 mg/day. During follow-up (6.9 ± 0.1 years), 340 (28%) had a clinically significant decline in 3MS score (≥1.5 SD of mean decline). After adjustment, dietary sodium intake was not associated with odds of cognitive decline (OR 0.96, 95% CI 0.50–1.84 per doubling of sodium). Similarly, potassium was not associated with cognitive decline; however, higher sodium:potassium intake was associated with increased odds of cognitive decline (OR 2.02 [95% CI 1.01–4.03] per unit increase). Neither sodium or potassium alone nor sodium:potassium were associated with micro- or macro-structural brain MRI indices. These results are limited by the use of FFQ. Conclusions: In community-dwelling older adults, higher sodium:potassium, but not sodium or potassium intake alone, was associated with decline in cognitive function, with no associations observed with micro- and macro-structural brain MRI indices. These findings do not support reduction dietary sodium/increased potassium intake to prevent cognitive decline with aging.