Non-dialysis Chronic Kidney Disease Research Articles

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

Effects of Cranberry Extract (Vaccinium macrocarpon) Supplementation on Lipid Peroxidation and Inflammation in Patients with Chronic Kidney Disease (Stages 3-4): A Randomized Controlled Trial

Background. Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD). Objectives. To evaluate cranberry (Vaccinium macrocarpon) supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. Design/Participants. A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. Measurements. The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method. Results. Twenty-five patients completed the study: 12 in the cranberry group (56.7 ± 7.5 years and body mass index (BMI) of 29.6 ± 5.5 kg/m2) and 13 in the placebo group (58.8 ± 5.1 years and BMI 29.8 ± 5.4 kg/m2). There were no differences in NF-kB or Nrf2 mRNA expressions (p=0.99 and p=0.89) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation. Conclusions. The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919.

Evaluation of Left Ventricular Flow Kinetic Energy by Four-Dimensional Blood Flow MRI in Nondialysis Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is associated with increased, and early cardiovascular disease risk. Changes in hemodynamics within the left ventricle (LV) respond to cardiac remodeling. The LV hemodynamics in nondialysis CKD patients are not clearly understood. To use four-dimensional blood flow MRI (4D flow MRI) to explore changes in LV kinetic energy (KE) and the relationship between LV KE and LV remodeling in CKD patients. Retrospective. 98 predialysis CKD patients (Stage 3: n = 21, stage 4: n = 21, and stage 5: n = 56) and 16 age- and sex-matched healthy controls. 3.0 T/balanced steady-state free precession (SSFP) cine sequence, 4D flow MRI with a fast field echo sequence, T1 mapping with a modified Look-Locker SSFP sequence, and T2 mapping with a gradient recalled and spin echo sequence. Demographic characteristics (age, sex, height, weight, blood pressure, heart rate, aortic regurgitation, and mitral regurgitation) and laboratory data (eGFR, Creatinine, hemoglobin, ferritin, transferrin saturation, potassium, and carbon dioxide bonding capacity) were extracted from patient records. Myocardial T1, T2, LV ejection fraction, end diastolic volume (EDV), end systolic volume, LV flow components (direct flow, delayed ejection, retained inflow, and residual volume) and KE parameters (peak systolic, systolic, diastolic, peak E-wave, peak A-wave, E/A ratio, and global) were assessed. The KE parameters were normalized to EDV (KEiEDV). Parameters were compared between disease stage in CKD patients, and between CKD patients and healthy controls. Differences in clinical and imaging parameters between groups were compared using one-way ANOVA, Kruskal Walls and Mann-Whitney U tests, chi-square test, and Fisher's exact test. Pearson or Spearman's correlation coefficients and multiple linear regression analysis were used to compare the correlation between LV KE and other clinical and functional parameters. A P-value of <0.05 was considered significant. Compared with healthy controls, peak systolic (24.76 ± 5.40 μJ/mL vs. 31.86 ± 13.18 μJ/mL), systolic (11.62 ± 2.29 μJ/mL vs. 15.27 ± 5.10 μJ/mL), diastolic (7.95 ± 1.92 μJ/mL vs. 13.33 ± 5.15 μJ/mL), peak A-wave (15.95 ± 4.86 μJ/mL vs. 31.98 ± 14.51 μJ/mL), and global KEiEDV (9.40 ± 1.64 μJ/mL vs. 14.02 ± 4.14 μJ/mL) were significantly increased and the KEiEDV E/A ratio (1.16 ± 0.67 vs. 0.69 ± 0.53) was significantly decreased in CKD patients. As the CKD stage progressed, both diastolic KEiEDV (10.45 ± 4.30 μJ/mL vs. 12.28 ± 4.85 μJ/mL vs. 14.80 ± 5.06 μJ/mL) and peak E-wave KEiEDV (15.30 ± 7.06 μJ/mL vs. 14.69 ± 8.20 μJ/mL vs. 19.33 ± 8.29 μJ/mL) increased significantly. In multiple regression analysis, global KEiEDV (β* = 0.505; β* = 0.328), and proportion of direct flow (β* = -0.376; β* = -0.410) demonstrated an independent association with T1 and T2 times. 4D flow MRI-derived LV KE parameters show altered LV adaptations in CKD patients and correlate independently with T1 and T2 mapping that may represent myocardial fibrosis and edema. Stage 3.

Assessment of vitamin D intake and supplementation in non-dialysis chronic kidney disease patients

Assessment of vitamin D intake and supplementation in non-dialysis chronic kidney disease patients

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Association of endothelial dysfunction and peripheral arterial disease with sarcopenia in chronic kidney disease.

Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0±11.8years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI<1.0 was classified as poor endothelial function, and an ABI<0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04±0.16 vs. 1.08±0.15, P=0.028 for the right ABI; 1.01±0.16 vs. 1.06±0.16, P=0.002 for the left ABI) and VRI (0.83±0.57 vs. 1.08±0.56, P<0.001) and had higher serum levels of ICAM-1 (P<0.001), VCAM-1 (P=0.003) and ET-1 (P=0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P=0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P=0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.

Role of Nutrients in Pediatric Non-Dialysis Chronic Kidney Disease: From Pathogenesis to Correct Supplementation.

Nutrition management is fundamental for children with chronic kidney disease (CKD). Fluid balance and low-protein and low-sodium diets are the more stressed fields from a nutritional point of view. At the same time, the role of micronutrients is often underestimated. Starting from the causes that could lead to potential micronutrient deficiencies in these patients, this review considers all micronutrients that could be administered in CKD to improve the prognosis of this disease.

Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

The relative potential contribution of volume load and vascular mechanisms to hypertension in non-dialysis and dialysis chronic kidney disease patients.

Hypertension is highly prevalent and particularly difficult to treat adequately in patients with chronic kidney disease (CKD). The relative contribution of volume overload and vascular mechanisms to blood pressure measures in CKD and whether these effects differ in non-dialysis compared to dialysis patients is unknown. We determined the potential impact of volume load (stroke volume) and vascular mechanisms (inverse of total arterial compliance (inv TAC) and systemic vascular resistance (SVR)) on mean and brachial and aortic systolic blood pressures in 67 non-dialysis and 48 dialysis chronic kidney disease (CKD) patients. Relationships were determined in confounder adjusted regression models. Stroke volume (p value = 0.003) was more strongly associated with mean arterial pressure than SVR (p value = 0.9) (p value for difference = 0.03). When stroke volume and SVR were entered in the same regression model (model R2 = 0.324), they contributed equally to the variation in mean arterial pressure (p value for difference = 0.5). Stroke volume (p value ≤ 0.002) and inv TAC (p value ≤ 0.001) contributed equally to the variation in systolic pressures (p value for difference ≥ 0.9). When stroke volume and inv TAC were entered in the same regression model (model R2 = 0.752 to 0.765), they contributed equally to the variation in systolic blood pressures (p value for difference = 0.7). Stroke volume, TAC and SVR were similar (p value ≥ 0.5) and associated to the same extent with blood pressure measures in non-dialysis and dialysis CKD patients (p value for difference ≥ 0.1). In receiver operator characteristic curve analysis, elevated systolic blood pressure was determined by stroke volume (p value = 0.005) and inv TAC (p value = 0.03) but not SVR (p value = 0.8). The calculated power of the study was 0.999 based on α = 0.05. The present investigation suggests that both volume load and vascular mechanisms should be considered in the management of hypertension among patients with CKD. The extent and relative potential impact of volume load and vascular mechanisms on blood pressure measures are as large in non-dialysis compared to dialysis CKD patients.

Myosteatosis and aortic calcium score on abdominal CT as prognostic markers in non-dialysis chronic kidney disease patients

We aimed to examine the relationship between abdominal computed tomography (CT)-based body composition data and both renal function decline and all-cause mortality in patients with non-dialysis chronic kidney disease (CKD). This retrospective study comprised non-dialysis CKD patients who underwent consecutive unenhanced abdominal CT between January 2010 and December 2011. CT-based body composition was measured using semiautomated method that included visceral fat, subcutaneous fat, skeletal muscle area and density, and abdominal aortic calcium score (AAS). Sarcopenia and myosteatosis were defined by decreased skeletal muscle index (SMI) and decreased skeletal muscle density, respectively, each with specific cutoffs. Risk factors for CKD progression and survival were identified using logistic regression and Cox proportional hazard regression models. Survival between groups based on myosteatosis and AAS was compared using the Kaplan–Meier curve. 149 patients (median age: 70 years) were included; 79 (53.0%) patients had sarcopenia and 112 (75.2%) had myosteatosis. The median AAS was 560.9 (interquartile range: 55.7–1478.3)/m2. The prognostic factors for CKD progression were myosteatosis [odds ratio (OR) = 4.31, p = 0.013] and high AAS (OR = 1.03, p = 0.001). Skeletal muscle density [hazard ratio (HR) = 0.93, p = 0.004] or myosteatosis (HR = 4.87, p = 0.032) and high AAS (HR = 1.02, p = 0.001) were independent factors for poor survival outcomes. The presence of myosteatosis and the high burden of aortic calcium were significant factors for CKD progression and survival in patients with non-dialysis CKD.

Correlation Between C4/IgG with Macroproteinuria in Chronic Kidney Disease: A Pilot Study.

Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria. Whether the ratio of complement and IgG is associated with macroproteinuria remains unknown. A total of 1013 non-dialysis chronic kidney disease (CKD) patients were recruited according to the electrical case records system with 268 patients who endured kidney biopsy. Patients were grouped via the estimated glomerular filtration rate or the levels of proteinuria determination. Biomarkers in different CKD groups or proteinuria groups were compared by one-way ANOVA or independent samples t-test. Pearson or spearman analysis was employed to analyze correlation between clinical indexes. Further, influence factor of macroproteinuria was studied by using binary logistic regression. The ROC curve was performed to explore probable predictive biomarker for macroproteinuria. No significant difference of complement C3 and C4 among CKD1 to CKD5 stages, while higher level of complement C4 in patients with macroproteinuria. Further, C4 had a positive correlation with proteinuria (r=0.255, p=0.006). After adjusted for age, IgA, IgM, triglyceride and HDL, a binary logistic regression model showed lnC4/IgG (OR=3.561, 95% CI 2.196-5.773, p<0.01), gender (OR=1.737, 95% CI 1.116-2.702, p=0.014), age (OR=0.983, 95% CI 0.969-0.997, p=0.014), and history of diabetes (OR=0.405, 95% CI 0.235-0.699, p<0.01) were independent influence factors of macroproteinuria. The area under the ROC curve was 0.77 (95% CI: 0.75-0.82, p<0.001) for C4/IgG. The analysis of ROC curves revealed a best cut-off for complement C4 was 0.024 and yielded a sensitivity of 71% and a specificity of 71%. The area under the ROC curve was 0.841 (95% CI: 0.735-0.946, p < 0.001) for C4/IgG in IgA nephropathy patients. The analysis of ROC curves revealed a best cut-off for complement C4/IgG was 0.026 and yielded a sensitivity of 75% and a specificity of 81.2%. The area under the ROC curve for C4/IgG in CKD1-5 stages were 0.772, 0.811, 0.785, 0.835, 0.674. Complement C4/IgG could be used to predict macroproteinuria.

Clinical Impacts of Urinary Neutrophil Gelatinase-Associated Lipocalin in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

Chronic kidney disease (CKD) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for renal injury. However, the association between urinary NGAL concentrations and renal and cardiovascular events in patients with CKD undergoing PCI has not been elucidated. This study investigated the clinical impact of urinary NGAL concentrations on renal and cardiovascular outcomes in patients with non-dialysis CKD undergoing PCI.Methods and Results: We enrolled 124 patients with non-dialysis CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective PCI. Patients were divided into low and high NGAL groups based on the median urinary NGAL concentration measured the day before PCI. Patients were monitored for renal and cardiovascular events during the 2-year follow-up period. Kaplan-Meier analyses showed that the incidence of renal and cardiovascular events was higher in the high than low NGAL group (log-rank P<0.001 and P=0.032, respectively). Multivariate Cox proportional hazards analyses revealed that urinary NGAL was an independent risk factor for renal (hazard ratio [HR] 4.790; 95% confidence interval [CI] 1.537-14.924; P=0.007) and cardiovascular (HR 2.938; 95% CI 1.034-8.347; P=0.043) events. Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

Association of deprivation and its individual domains on outcomes in people with chronic kidney disease

Abstract Background Due to the high correlation of chronic kidney disease (CKD) with other co-morbidities, the sole effect of CKD on deprived people is not clear. In addition, there is a paucity of evidence in the literature linking isolated domains of deprivation to outcomes. This study aimed to examine whether deprivation was associated with adverse outcomes in patients with CKD, independent of cardiometabolic morbidities. Individual domains of deprivation were also evaluated. Methods A retrospective study of patients with non-dialysis CKD (ND-CKD) in the Salford Kidney Study to investigate the association of deprivation with outcomes. The English Indices of Deprivation was used for the comparative analysis of the five quintiles of deprivation. Two propensity score methods were used to attenuate the confounding effect of cardiometabolic morbidities between the least and the most deprived groups. Results People living in the least deprived areas (n=319) had a lower risk of combined outcomes (all-cause mortality and renal replacement therapy) when compared to the most deprived group (n=813), HR 0.83; 95% CI 0.71-0.98. The negative association of deprivation remained after matching but with mixed statistical significance, when using different propensity methods, (HR 0.85; 95% CI 0.70-1.03 for propensity score matching and HR 0.77; 95% CI 0.61-0.98 for inverse probability weighting). The association of combined outcomes varied across component IMD domains with wide confidence intervals. However, areas with lower scores for education, income, and employment were significantly associated with a higher risk. Conclusions This study has identified that in people with ND-CKD, unemployment, poor educational attainment and lower household income were associated with poor outcomes. The association of deprivation with adverse outcomes persists despite adjustment for cardiometabolic morbidities.

A Klotho-Based Machine Learning Model for Prediction of both Kidney and Cardiovascular Outcomes in Chronic Kidney Disease

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; This study aimed to develop and validate machine learning (ML) models based on serum Klotho for predicting end-stage kidney disease (ESKD) and cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Five different ML models were trained to predict the risk of ESKD and CVD at three different time points (3, 5, and 8 years) using a cohort of 400 non-dialysis CKD patients. The dataset was divided into a training set (70%) and an internal validation set (30%). These models were informed by data comprising 47 clinical features, including serum Klotho. The best-performing model was selected and used to identify risk factors for each outcome. Model performance was assessed using various metrics. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The findings showed that the least absolute shrinkage and selection operator regression model had the highest accuracy (C-index = 0.71) in predicting ESKD. The features mainly included in this model were estimated glomerular filtration rate, 24-h urinary microalbumin, serum albumin, phosphate, parathyroid hormone, and serum Klotho, which achieved the highest area under the curve (AUC) of 0.930 (95% CI: 0.897–0.962). In addition, for the CVD risk prediction, the random survival forest model with the highest accuracy (C-index = 0.66) was selected and achieved the highest AUC of 0.782 (95% CI: 0.633–0.930). The features mainly included in this model were age, history of primary hypertension, calcium, tumor necrosis factor-alpha, and serum Klotho. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; We successfully developed and validated Klotho-based ML risk prediction models for CVD and ESKD in CKD patients with good performance, indicating their high clinical utility.

Association between short-term blood pressure variability and target organ damage in non-dialysis patients with chronic kidney disease

BackgroundIt is unclear whether short-term blood pressure variability (BPV) is associated with target organ damage in patients with non-dialysis chronic kidney disease (CKD).MethodsA cross-sectional, single-center study was conducted among 3442 non-dialysis CKD patients hospitalized in the department of Nephrology of the Fifth Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2022 and collected the demographic, laboratory, clinic blood pressure, ambulatory blood pressure data, and short-term BPV assessed by the weighted standard deviation (wSD) derived from ambulatory blood pressure monitoring (ABPM). Multivariate logistic analyses were used to evaluate the independent effects between short-term BPV and subclinical target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria.ResultsThe average age of the participants was 47.53 ± 14.06 years and 56% of participants were male. The baseline eGFR was 69 mL/min/1.73 m2. Based on the tertile distribution of wSD according to equal numbers, patients were divided into three categories with T1(< 9.66 mmHg), T2(9.66–12.23 mmHg), and T3(> 12.23 mmHg) of SBPV; T1(< 8.17 mmHg), T2(8.17–9.93 mmHg), and T3(> 9.93 mmHg) of DBPV. The participants with the higher wSD group had a higher prevalence of target organ damage than their counterparts (P-trend < 0.05). An increasing trend in short-term variability was present with advancing CKD stages (P-trend < 0.001). Multivariate logistic analyses results showed that the odds ratio (OR) of SBP wSD was (1.07 [1.03,1.11], P < 0.001) for LVH, (1.04 [1.01,1.07, P = 0.029) for abnormal CIMT, (1.05 [1.02,1.08], P = 0.002) for low eGFR, and (1.06 [1.02,1.09], P = 0.002) for albuminuria; The OR of DBP wSD was (1.07 [1.02,1.12], P = 0.005) for LVH, (1.05 [1.01,1.09], P = 0.028) for abnormal CIMT, (1.05 [1.01,1.09], P = 0.022) for low eGFR, and (1.05 [1.01,1.10], P = 0.025) for albuminuria when adjusted for confounding factors and mean BP.ConclusionsIn conclusion, short-term BPV is associated with target organ damage, and irresponsible of average blood pressure levels, in Chinese non-dialysis CKD participants.

Clinical effect of roxadustat vs. erythropoietin in non-dialysis CKD with diabetes: a single center propensity score matching analysis.

Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients. Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05). After 4, 12, and 24weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5g/L, 104g/L, and 106.5g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91g/L, 94.5g/L, and 94.5g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels. In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels.

Relationship between serum phosphorus and mortality in non-dialysis chronic kidney disease patients: evidence from NHANES 2001–2018

BackgroundHyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those with preserved kidney function, remains uncertain.MethodsA prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (2001–2008). Serum phosphorus was analyzed as a continuous variable, or categorized into three groups: < 3.5 mg/dL, 3.5 to < 4.5 mg/dL, and ≥ 4.5 mg/dL. Cox proportional hazards models were used to analyze the association between phosphorus with all-cause and cardiovascular disease (CVD) mortality, with or without adjustment for age, sex, race, hemoglobin, estimated glomerular filtration rate (eGFR), serum albumin, serum calcium, 25(OH)D, obesity, hypertension, diabetes, and CVD.ResultsA total of 7694 participants were included in the analysis, representing 28 million CKD patients in the United States. During mean 92 months of follow up, 2708 all-cause deaths (including 969 CVD deaths) were observed. Per 1 mg/dL increase in phosphorus was associated with a 13% and 24% increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95%CI, 1.02–1.24) and CVD mortality (HR, 1.24; 95%CI, 1.07–1.45), respectively. Compared with the < 3.5 mg/dL, phosphorus ≥ 4.5 mg/dL was associated with a 28% and 57% increased risk of all-cause mortality (HR, 1.28; 95%CI, 1.05–1.55) and CVD mortality (HR, 1.57; 95CI, 1.19–2.08), respectively. In participants with eGFR < 60 ml/min/1.73m2, elevated phosphorus (≥ 4.5 mg/ dL) were significantly associated with increased risk of all-cause mortality (HR, 1.36; 95%CI, 1.07–1.72). No significant association was observed in eGFR ≥ 60 ml/min/1.73m2 group (HR, 1.31; 95%CI, 0.86–1.99). This correlation does not differ significantly between subgroups defined by eGFR level (P for interaction = 0.889).ConclusionSerum phosphorus above 4.5 mg/dL is significantly associated with a 28% and 57% increased risk of all-cause and CVD death in non-dialysis CKD patients, respectively. This relationship still demonstrated in patients with eGFR < 60 ml/min/1.73m2. However, for population with eGFR ≥ 60 ml/min/1.73m2, further verification is needed.

Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study

Rationale & ObjectiveHbA1c is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis dependent CKD population remains unknown. Study DesignProspective cohort study. Setting& Participants: 3110 participants with CKD from the Chronic Renal Insufficiency Cohort study. ExposureBaseline GA levels. OutcomesIncident end-stage kidney disease (ESKD), cardiovascular disease (CVD) events, and all-cause mortality. Analytical ApproachCox proportional hazards regression. ResultsParticipant characteristics included mean age 59.0 (SD 10.8) years; 1357 (43.6%) female; 1550 (49.8%) with diabetes. The median GA was 18.7 (interquartile range, 15.8-23.3)%. During an average 7.9-year follow-up, there were 980 ESKD events, 968 CVD events, and 1084 deaths. Higher GA levels were associated with greater risks of all outcomes, regardless of diabetes status: hazard ratios for ESKD, CVD, and death among participants with the highest quartile compared with quartile 2 (reference) were 1.42 (95%CI, 1.19-1.69), 1.67 (CI, 1.39-2.01), and 1.63 (CI, 1.37-1.94), respectively. The associations with CVD and death appeared J-shaped, with increased risk also seen at the lowest GA levels. Among patients with coexisting CKD and diabetes, the associations of GA with outcomes remained significant even after adjusting for HbA1c. For each outcome, we observed a significant increase in the fraction of new prognostic information when both GA and HbA1c were added to models. LimitationsLack of longitudinal GA measurements; HbA1c measurements were largely unavailable in participants without diabetes. ConclusionsAmong patients with CKD, GA levels were independently associated with risks of ESKD, CVD, and mortality, regardless of diabetes status. GA added prognostic value to HbA1c among patients with coexisting CKD and diabetes.

The association between peripheral eosinophil count and chronic kidney disease: evidence from NHANES 1999–2018

Background Renal impairment has been previously linked to peripheral eosinophil count (PEC), prompting an investigation into its potential relationship with chronic kidney disease (CKD). This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES 1999–2018) to comprehensively explore the association between PEC and CKD. Methods Survey-weighted generalized multivariate linear regression was employed to evaluate the associations between PEC, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), with meticulous adjustment for potential covariates. To assess non-linear correlations, a restricted cubic spline analysis was conducted. Sensitivity analysis was performed to test the stability of results. Results The study included a total of 9224 participants with non-dialysis CKD. In the multivariate linear regression model, after comprehensive adjustment for potential covariates, PEC showed a negative association with eGFR (β per 100 cells/uL increase in PEC, −0.71; 95% CI, −1.04, −0.37), while demonstrating a positive trend with UACR (β per 100 cells/uL increase in PEC, 10.21; 95% CI, 1.37, 19.06). The restrictive cubic spline curve analysis suggested that these associations occurred within the range of 0 to 400 cells/uL for PEC. Sensitivity analysis supported the stability of the observed results. Conclusions Circulating eosinophil levels are negatively correlated with eGFR and demonstrate a positive trend with UACR, when PEC falls within the range of less than 400 cells/uL among adults with CKD. Further research is warranted to validate these findings.

The differential effect of modern intravenous iron on fibroblast growth factor 23 and phosphate in non-dialysis dependent CKD – the exploratory randomized controlled double-blind ExplorIRON-CKD study

BackgroundIntravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover.MethodsThe single-center double-blind randomized controlled trial “Iron and Phosphaturia – ExplorIRON-CKD” primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1–2 days following iron administration, 2 weeks, 1 month (second iron administration), 1–2 days following second administration, 2 months and 3 months following initial infusion.ResultsTwenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1–2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1–203.1) %; p < 0.001 and Baseline to 1–2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 – 25.4) % vs. FCM: 235.1 (138.5–434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI.ConclusionsThe study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds.Trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019–004370-26 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB) (First date of trial registration: 03/12/2019).