The correlation of low serum albumin with mortality in patients with chronic kidney disease (CKD) is partly linked to its association with systemic inflammation. However, it is not clear to what ...extent albumin's correlation with mortality depends on concomitant systemic inflammation. Here we addressed this question in patients with CKD stage 5.
Serum albumin (S-Alb), systemic inflammation (high-sensitive C-reactive protein, hsCRP), cardiovascular disease (CVD) and nutritional status (subjective global assessment, SGA) were assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent hemodialysis (HD) and 87 prevalent peritoneal dialysis (PD) patients. Patients were divided into four groups according to hsCRP and S-Alb in each cohort: Group 1 -normal S-Alb and normal hsCRP (reference); Group 2 -low S-Alb and normal hsCRP; Group 3-normal S-Alb and high hsCRP; Group 4-low S-Alb and high hsCRP. Survival over 60 months was analyzed.
In Cox analysis, Group 4 had an increased mortality risk (adjusted Hazard ratio (95% confidence interval): 1.62 (1.06-2.47); p = 0.02) whereas the augmented mortality risks for Groups 2 and 3 in univariate analyses were not significant after adjustments for age, gender, blood pressure, diabetes mellitus, smoking, SGA, renal function and renal replacement technique.
Whereas mortality risk was increased in CKD stage 5 patients with low S-Alb and high CRP, it was not increased in patients with low S-Alb and normal CRP. Our observation suggests that inflammatory status should be taken into account when using S-albumin for risk assessment in CKD stage 5 patients.
Contemporary data on the prevalence and incidence of aortic stenosis (AS) and aortic valve replacement (AVR) in patients initiating dialysis are scarce. This observational cohort study aimed to ...estimate (1) the point prevalence of AS and AVR at dialysis start and (2) the AS incidence and associated factors prospective to dialysis initiation. The study included 14,550 patients initiating dialysis registered in the Swedish Renal Registry between 2005 and 2018. AS was defined by the International Statistical Classification of Diseases, Tenth Revision codes, and AVR by the surgical procedure codes. Associations between covariates and outcomes were assessed in Cox regression models. The median age was 68 (57 to 77), 66% were males, and the point prevalence of AS and AVR was 3.4% and 1.1%, respectively. In those without known AS/AVR at dialysis initiation (n = 14,050), AS was diagnosed in 595 patients (incidence 16.3/1000 person-years, 95% confidence interval CI 15.1 to 17.7/1,000 person-years) during a median follow-up of 2.7 years (interquartile range 1.1 to 5.7). In adjusted Cox regression models, higher age (hazard ratio HR 1.03, 95% CI 1.02 to 1.04), male gender (HR 1.51, 95% CI 1.25 to 1.83), atrial fibrillation (HR 1.32, 95% CI 1.06 to 1.64), and hypertension (HR 1.65, 95% CI 1.03 to 2.65) were associated with incident AS. Peritoneal dialysis patients had a nonsignificant trend toward higher AS risk compared with hemodialysis (HR 1.18, 95% CI 0.99 to 1.40). About 20% of patients (n = 113) diagnosed with incident AS underwent AVR (incidence 3.1/1000 person-years, 95% CI 2.6 to 3.7/1,000). Only the male gender was associated with AVR (HR 2.07, 95% CI 1.30 to 3.30). In conclusion, the prevalence and incidence of AS and AVR in patients initiating dialysis are high. A fifth of newly diagnosed AS underwent AVR after dialysis onset.
Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental ...iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.
Serum albumin is a widely used biomarker of nutritional status in patients with CKD; however, its usefulness is debated. This study investigated serum albumin and its correlation with several markers ...of nutritional status in incident and prevalent dialysis patients.
In a cross sectional study, serum albumin (bromocresol purple), and other biochemical (serum creatinine), clinical (subjective global assessment SGA), anthropometric (handgrip strength, skinfold thicknesses), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status were assessed in 458 incident (61% male; mean age 54 +/- 13 years; GFR, 6.6 +/-2.3 ml/min per 1.73 m(2); recruited 1994–2010) and 383 prevalent (56% male; mean age 62 +/- 14 years; recruited 1989–2004) dialysis patients.
In incident patients: serum albumin was correlated with sex (beta = -0.13; P = 0.02), diabetes mellitus (beta = -0.18; P = 0.004), and urinary albumin excretion (beta = -0.42; P = 0.001) but less so with poor nutritional status (SGA score >1; beta = -0.19; P = 0.001). In prevalent patients, serum albumin was correlated with age (beta = -0.14; P = 0.05), high-sensitivity C-reactive protein (beta = -0.34; P = 0.001), diabetes mellitus (beta = -0.11; P = 0.04), and SGA score >1 (beta = -0.14; P = 0.003). In predicting nutritional status assessed by SGA and other markers, adding serum albumin to models that included age, sex, diabetes, and cardiovascular disease did not significantly increase explanatory power.
In incident and prevalent dialysis patients,serum albumin correlates poorly with several markers of nutritional status. Thus, its value as a reliable marker of nutritional status in patients with ESRD is limited. In addition, the following inconsistencies between the main text and Tables 1 and 3 are also corrected as follows. (1) In Table 1, the GFR initially written as 6 +/- 3 ml/min per 1.73(2) should be corrected to 6.6 +/- 2.3 ml/min per 1.73(2). (2) On line 11 of page 1448, under the Clinical Correlates of Serum Albumin Concentration section describing the multiple regression models (Table 3), the P value was initially written as“serum albumin was associated with age (beta = -0.14; P = 0.05).” The P value should be corrected to have the same value as that given in Table 3 (beta = -0.14; P = 0.005. corrected.
Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anaemia in CKD patients. These guidelines addressed ...all of the important points related to anaemia management in CKD patients, including therapy with erythropoieis stimulating agents (ESA), iron therapy, ESA resistance and blood transfusion use. Because most guidelines were 'soft' rather than 'strong', and because global guidelines need to be adapted and implemented into the regional context where they are used, on behalf of the European Renal Best Practice Advisory Board some of its members, and other external experts in this field, who were not participants in the KDIGO guidelines group, were invited to participate in this anaemia working group to examine and comment on the KDIGO documents in this position paper. In this article, the group concentrated only on those guidelines which we considered worth amending or adapting. All guidelines not specifically mentioned are fully endorsed.
Background
It is unknown whether renal dysfunction conveys poor anticoagulation control in warfarin‐treated patients with atrial fibrillation and whether poor anticoagulation control associates with ...the risk of adverse outcomes in these patients.
Methods and Results
This was an observational study from the Stockholm CREatinine Measurements (SCREAM) cohort including all newly diagnosed atrial fibrillation patients initiating treatment with warfarin (n=7738) in Stockholm, Sweden, between 2006 and 2011. Estimated glomerular filtration rate (eGFR; mL/min per 1.73 m2) was calculated from serum creatinine. Time‐in‐therapeutic range (TTR) was assessed from international normalized ratio (INR) measurements up to warfarin cessation, adverse event, or end of follow‐up (2 years). Adverse events considered a composite of intracranial hemorrhage, ischemic stroke, myocardial infarction, or death. During median 254 days, TTR was 83%, based on median 21 INR measurements per patient. TTR was 70% among patients with eGFR <30, around 10% lower than in those with normal renal function. During observation, adverse events occurred in 4.0% of patients, and those with TTR ≤75% were at higher adverse event risk. This was independent of patient characteristics, comorbidities, number of INR tests, days exposed to warfarin, and, notably, independent of eGFR: adjusted odds ratio (OR) 1.84 (95% CI, 1.41–2.40) for TTR 75% to 60% and adjusted OR 2.09 (1.59–2.74) for TTR <60%. No interaction was observed between eGFR and TTR in association to adverse events (P=0.2).
Conclusion
Severe chronic kidney disease (eGFR <30) patients with atrial fibrillation have worse INR control while on warfarin. An optimal TTR (>75%) is associated with lower risk of adverse events, independently of underlying renal function.
Background Patients with chronic kidney disease stage 5 have high comorbidity and are prone to inflammation that may contribute to the high cardiovascular mortality risk. Study Design Three-month ...observational cohort study of prevalent hemodialysis patients. Settings & Participants 228 hemodialysis patients (44% women) were included, median age of 66 years, median time on dialysis therapy of 29 months. Predictors & Outcomes In part 1, comorbidity and intercurrent illness were predictors and C-reactive protein (CRP) level was the outcome. In part 2, serial CRP values were predictors and survival was the outcome. Measurements High-sensitivity CRP was measured weekly and interleukin 6 (IL-6), tumor necrosis factor α, and IL-10 were measured monthly. Data for comorbidity were collected from patient records to calculate Davies comorbidity score, and self-reported clinical events were recorded weekly. Results Median baseline CRP level was 6.7 mg/L (25th to 75th percentiles, 2.5 to 21 mg/L). Baseline CRP level correlated with time-averaged CRP (Spearman ρ = 0.76) and individual median of serial CRP values (ρ = 0.78; both P < 0.001). Part 1: comorbidity score was significantly associated with greater CRP and IL-6 levels. Age, sex, comorbidity, and 7 of 12 clinical events had significant effects on CRP level variation. Part 2: during a mean follow-up of 29 months, 38% of patients died. Median and mean serial CRP levels were associated with a greater hazard ratio for death (1.013; 95% confidence interval, 1.004 to 1.022) and 1.012 (95% confidence interval, 1.004 to 1.020) than baseline, maximum, and minimum CRP values during the study. Other significant covariates were age, Davies risk group, dialysis vintage, and albumin level. Limitations The study is based on observational data for prevalent dialysis patients. Conclusions Comorbidity and clinical events are strongly associated with inflammation in hemodialysis patients. Despite variability over time, inflammation assessed by using CRP level is a strong predictor of mortality. Serial measurements provide additional information compared with a single measurement.
Summary Background & aims Muscle wasting is considered the best marker of protein-energy wasting in end-stage renal disease (ESRD). We tested the usefulness of a simple observer subjective muscle ...atrophy (MA) grading in relation to morbidity and mortality in ESRD patients. Methods In two different ESRD cohorts (265 incident patients starting dialysis and 221 prevalent hemodialysis patients), each patient's degree of MA was visually graded by a trained nurse on a scale from 1 to 4 as part of the subjective global assessment. This score was confronted with inflammatory and nutritional indexes as well as objective measurements of muscle atrophy. Patients were then prospectively followed for up to four or six years, depending on the cohort. Results Thirty percent of the incident and 39% of the prevalent patients presented signs of MA. Across worsening MA scale, nutritional and anthropometric markers of muscle loss were incrementally poorer. Inflammation markers as well as the proportion of women became progressively higher. Female sex, presence of cardiovascular disease, inflammation and low insulin-like growth factor-1 levels were associated with increased significant odd ratios of MA in each cohort. After adjustment for age, sex, inflammation, diabetes, cardiovascular disease, glomerular filtration rate and/or time on hemodialysis, the hazard ratio of death for moderate/severe MA was 2.62 (95% CI: 1.34, 5.13; p = 0.001) and 3.04 (95% CI: 1.61, 5.71; p = 0.0001) in the incident and prevalent cohorts respectively. Conclusion Increased MA is more common in female dialysis patients and associated with inflammation, poor nutritional and anthropometric status, as well as a 3-fold increased 4–6 year mortality. Our data support the use of frequent MA and/or nutritional assessments in the clinical practice.
Background
Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast ...growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD.
Methods
This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8–18.8 years, glomerular filtration rate (GFR) range 9–68 mL/min/1.73 m
2
) and 43 transplanted patients (CKD-T; age range 3.3–17.7 years, GFR range 10–99 mL/min/1.73 m
2
) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI).
Results
The prevalence of high FGF23 levels (≥95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during follow-up in CKD and CKD-T patients (β = −0.2,
p
< 0.001). A high log FGF23
z
-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (β = 1.8,
p
= 0.06). In addition, high log FGF23 (β = −0.43,
p
= 0.01) and low log Klotho (β = 0.44,
p
= 0.006) over time were associated with a worse left ventricular diastolic function (cc-TDI e′/a′) in CKD-T patients.
Conclusions
In pediatric CKD and CKD-T patients, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation.
Hepcidin is considered to play a central role in the pathophysiology of renal anemia. Recent studies in healthy individuals have demonstrated a suppressive effect of vitamin D (VD) on the expression ...of hepcidin. In this post-hoc analysis based on a randomized controlled study, we evaluated the effect of supplementing chronic kidney disease (CKD) patients (stage G3-G4) with a high daily dose of native VD on serum levels of hepcidin-25, the hepcidin/ferritin ratio, as well as on markers of erythropoiesis.
Patients with CKD stage G3-G4 included in a double blind, randomized, placebo (PBO) controlled study with available hepcidin measurements were analyzed. Study subjects received either 8000 international units (IU) of cholecalciferol daily or PBO for 12 weeks. We evaluated the change in markers of hepcidin expression, erythropoiesis, and iron status from baseline to week 12 and compared the change between the groups.
Eighty five patients completed the study. Calcitriol, but not 25-hydroxyvitamin D (25(OH) D), was inversely correlated with serum levels of hepcidin-25 (rho = -0,38; p = < 0, 01 and rho = -0,02; p = 0, 89, respectively) at baseline. Supplementation with VD significantly raised the serum concentration of serum 25(OH)D in the treatment group (from 54 (39-71) to 156 (120-190) nmol/L; p = < 0, 01)) but had no effect on any of the markers of hepcidin, erythropoiesis, or iron status in the entire cohort. However, we did observe an increase in hemoglobin (HB) levels and transferrin saturation (TSAT) as compared to the PBO group in a subgroup of patients with low baseline 25(OH)D levels (< 56 nmol/L). In contrast, in patients with high baseline 25(OH)D values (≥ 56 nmol/L), VD supplementation associated with a decrease in HB levels and TSAT (p = 0,056) within the VD group in addition to a decrease in hepcidin levels as compared to the PBO group.
High-dose VD supplementation had no discernible effect on markers of hepcidin or erythropoiesis in the entire study cohort. However, in patients with low baseline 25(OH)D levels, high-dose VD supplementation associated with beneficial effects on erythropoiesis and iron availability. In contrast, in patients with elevated baseline 25(OH)D levels, high-dose VD supplementation resulted in a decrease in hepcidin levels, most likely due to a deterioration in iron status.
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