Dialysis Modality and Incident Stroke Among Patients With End-Stage Kidney Disease: A Registry-Based Cohort Study.

BACKGROUND: Patients with end-stage kidney disease undergoing dialysis are at significant risk of stroke. Whether dialysis modality is associated with cerebrovascular disease is unclear. This study compared the risk of incident stroke in patients undergoing peritoneal dialysis or hemodialysis. METHODS: Thirty-nine thousand five hundred forty-two patients without a history of stroke who initiated dialysis between January 1, 2010, and December 31, 2014 were retrospectively studied using Taiwan's National Health Insurance Research Database. We matched 3809 patients undergoing peritoneal dialysis (mean age 59±13 years; 46.5% women) and 11 427 patients undergoing hemodialysis (mean age 59±13 years; 47.3% women) by propensity score in a 1:3 ratio with follow-up through December 31, 2015. The primary outcome was incident acute ischemic stroke. Secondary outcomes included hemorrhagic stroke, acute coronary syndrome, and all-cause mortality. Cox proportional hazard models were conducted to determine hazard ratios of clinical outcomes according to the dialysis modality. RESULTS: During a median follow-up of 2.59 (interquartile range 1.50-3.93) years, acute ischemic stroke, hemorrhagic stroke, and acute coronary syndrome occurred in 783 (5.1%), 376 (2.5%), and 1350 (8.9%) patients, respectively. In a multivariable Cox model that accounted for the competing risk of death, acute ischemic stroke occurred more frequently in the peritoneal dialysis group than in the hemodialysis group (subdistribution hazard ratio, 1.32 [95% CI, 1.13-1.54]; P=0.0005). There were no significant treatment-related differences in the risk of hemorrhagic stroke (subdistribution hazard ratio, 0.89 [95% CI, 0.70-1.14]; P=0.3571) and acute coronary syndrome (subdistribution hazard ratio, 0.99 [95% CI, 0.88-1.12]; P=0.9080). Patients undergoing peritoneal dialysis were more likely to die from any cause than patients undergoing hemodialysis (adjusted hazard ratio, 1.24 [95% CI, 1.15-1.33]; P<0.0001). CONCLUSIONS: Peritoneal dialysis was associated with a significantly increased risk of acute ischemic stroke compared with hemodialysis. Further studies are needed to clarify whether more aggressive cerebrovascular preventive strategies might mitigate the excess risk for ischemic stroke among patients receiving peritoneal dialysis.

The Potential Influence of Uremic Toxins on the Homeostasis of Bones and Muscles in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) often experience a high accumulation of protein-bound uremic toxins (PBUTs), specifically indoxyl sulfate (IS) and p-cresyl sulfate (pCS). In the early stages of CKD, the buildup of PBUTs inhibits bone and muscle function. As CKD progresses, elevated PBUT levels further hinder bone turnover and exacerbate muscle wasting. In the late stage of CKD, hyperparathyroidism worsens PBUT-induced muscle damage but can improve low bone turnover. PBUTs play a significant role in reducing both the quantity and quality of bone by affecting osteoblast and osteoclast lineage. IS, in particular, interferes with osteoblastogenesis by activating aryl hydrocarbon receptor (AhR) signaling, which reduces the expression of Runx2 and impedes osteoblast differentiation. High PBUT levels can also reduce calcitriol production, increase the expression of Wnt antagonists (SOST, DKK1), and decrease klotho expression, all of which contribute to low bone turnover disorders. Furthermore, PBUT accumulation leads to continuous muscle protein breakdown through the excessive production of reactive oxygen species (ROS) and inflammatory cytokines. Interactions between muscles and bones, mediated by various factors released from individual tissues, play a crucial role in the mutual modulation of bone and muscle in CKD. Exercise and nutritional therapy have the potential to yield favorable outcomes. Understanding the underlying mechanisms of bone and muscle loss in CKD can aid in developing new therapies for musculoskeletal diseases, particularly those related to bone loss and muscle wasting.

Aging is associated with slower renal progression in patients with chronic kidney disease.

Objectives: Chronic kidney disease (CKD) is prevalent among the elderly. However, little is known about how the clinical course of CKD vary with age. The purpose of this study was to examine the impact of aging on the risk of end-stage kidney disease (ESKD) in patients with moderate to advanced CKD. Materials and Methods: A total of 454 patients with stages 3-5 CKD were prospectively followed for a median of 5.1 years. The primary outcome was ESKD needing chronic dialysis therapy or preemptive kidney transplantation. The secondary outcome was a composite of ESKD or all-cause mortality. Results: The mean age of the patients was 65 ± 13 years. 65.4% were men, 44.9% had diabetes mellitus, and 22.7% had cardiovascular disease. Overall, 142 participants progressed to ESKD and 63 participants died. Compared with young patients (age <65 years, n = 205), elderly patients (age ≥65 years, n = 249) were associated with a significantly decreased risk of ESKD in Cox proportional hazards models adjusted for sex, smoking history, diabetes mellitus, cardiovascular disease, systolic blood pressure, estimated glomerular filtration rate, urine protein: Creatinine ratio, use of renin-angiotensin-aldosterone blocker, hemoglobin, phosphate, interleukin-6, body mass index, and N-terminal pro-brain natriuretic peptide (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.45, 0.96; P = 0.028). The results remained statistically significant when death as a competing risk was taken into account (subdistribution HR: 0.65; 95% CI: 0.45, 0.95, P = 0.026). Notably, elderly did not predict a higher risk for the composite outcome (HR: 0.94; 95% CI: 0.67, 1.32; P = 0.723). Conclusion: Elderly confers a decreased risk of ESKD in Taiwanese patients with moderate to advanced CKD. Our findings suggest that age is an important effect modifier for CKD progression.

Education and Protein Supplementation Improve Nutritional Biomarkers among Hypoalbuminemic Peritoneal Dialysis Patients: A Quasi-Experimental Design.

Protein-energy wasting is prevalent in peritoneal dialysis patients, which causes a heavy burden for individuals and healthcare systems. We aimed to investigate the effect of nutritional education, and/or protein supplementation on nutritional biomarkers in hypoalbuminemic peritoneal dialysis patients. A quasi-experimental study was conducted in two dialysis centers at Taipei Tzu Chi Hospital and Shin Kong Wu Ho-Su Memorial Hospital. Patients were allocated in three groups including control (n = 12), milk protein (n = 21) and soy protein (n = 20). All patients received dietary guidelines from dietitians and completed 3-day dietary records during monthly visits for consecutive three months. Nutrients were analyzed using Nutritionist Professional software. Blood urea nitrogen (BUN), creatinine, albumin, total protein, hemoglobin, serum calcium, phosphorus, sodium, and potassium were assessed monthly. Total cholesterol and triglycerides were measured every three months. After three-month intervention, protein intake (percent of total calories), and serum albumin were significantly increased in three groups. Protein, phosphorus intake, and BUN were increased in two intervention groups. Total serum protein increased in control and milk protein groups, and creatinine increased the control group. Serum phosphorus was not significantly changed. Nutritional education alone, or combined with protein supplementation, significantly improve protein intake, and nutritional status by increasing serum albumin, but not serum phosphorus in hypoalbuminemic peritoneal dialysis patients.

Body composition is associated with clinical outcomes in patients with non-dialysis-dependent chronic kidney disease.

An inverse relationship between body mass index (BMI) and mortality (the obesity paradox) has been found in patients with non-dialysis-dependent chronic kidney disease (CKD). However, it is unclear whether increased muscle mass or body fat confers the survival advantage. To resolve this we investigated the impact of body makeup on a composite outcome of death or cardiovascular events in a prospective cohort of 326 patients with stage 3-5 CKD not yet on dialysis. Lean mass and body fat were determined using the Body Composition Monitor, a multifrequency bioimpedance spectroscopy device, and were expressed as the lean tissue or fat tissue index, respectively. Patients were stratified as High (above median) or Low (below median) BMI, High or Low lean tissue index, or as High or Low fat tissue index. During a median follow-up of 4.6 years, there were 40 deaths and 68 cardiovascular events. In Cox proportional hazards models, a High lean tissue index, but not High BMI or High fat tissue index, predicted a lower risk of both the composite or its component outcomes (reference: below median). When patients were further stratified into four distinct body composition groups based on both the lean and fat tissue index, only the High lean/fat tissue index group had a significantly lower risk of the composite outcome (hazard ratio 0.36, 95% confidence interval 0.14-0.87; reference: Low lean/fat tissue index group). Thus, the lean tissue index can provide better risk prediction than the BMI alone in non-dialysis-dependent patients with CKD. The High lean/fat tissue index appears to be associated with best outcomes. An optimal body composition for improving the prognosis of CKD needs to be determined.

Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease.

Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years) with stage 3-5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height²). An LTI of less than 10% of the normal value (low LTI) indicates muscle wasting. Patients with low LTI (n = 40) tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3-5 CKD.

Association of fluid retention with anemia and clinical outcomes among patients with chronic kidney disease.

BACKGROUND: Observational studies have demonstrated an association between anemia and adverse outcomes in patients with chronic kidney disease (CKD). However, randomized trials failed to identify a benefit of higher hemoglobin concentrations, suggesting that the anemia-outcome association may be confounded by unknown factors. METHODS AND RESULTS: We evaluated the influence of fluid status on hemoglobin concentrations and the cardiovascular and renal outcomes in a prospective cohort of 326 patients with stage 3 to 5 CKD. Fluid status, as defined by overhydration (OH) level measured with bioimpedance, was negatively correlated with hemoglobin concentrations at baseline (r=-0.438, P<0.001). In multivariate regression analysis, OH remained an independent predictor of hemoglobin, second only to estimated glomerular filtration rate. Patients were stratified into 3 groups: no anemia (n=105), true anemia (n=82), and anemia with excess OH (n=139) (relative OH level ≥7%, the 90th percentile for the healthy population). During a median follow-up of 2.2 years, there was no difference in cardiovascular and renal risks between patients with true anemia and those with no anemia in the adjusted Cox proportional hazards models. However, patients with anemia with excess OH had a significantly increased risk of cardiovascular morbidity and mortality and CKD progression relative to those with true anemia and those with no anemia, respectively. CONCLUSIONS: Fluid retention is associated with the severity of anemia and adverse cardiovascular and renal outcomes in patients with CKD. Further research is warranted to clarify whether the correction of fluid retention, instead of increasing erythropoiesis, would improve outcomes of CKD-associated anemia.

Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease.

Volume overload is a predictor of mortality in dialysis patients. However, the fluid status of patients with chronic kidney disease (CKD) but not yet on dialysis has not been accurately characterized. We used the Body Composition Monitor, a multifrequency bioimpedance device, to measure the level of overhydration in CKD patients, focusing on the association between overhydration and cardiovascular disease risk factors. Overhydration was the difference between the amount of extracellular water measured by the Body Composition Monitor and the amount of water predicted under healthy euvolemic conditions. Volume overload was defined as an overhydration value at and above the 90th percentile for the normal population. Of the 338 patients with stages 3-5 CKD, only 48% were euvolemic. Patients with volume overload were found to use significantly more antihypertensive medications and diuretics but had higher systolic blood pressures and an increased arterial stiffness than patients without volume overload. In a multivariate analysis, male sex, diabetes, pre-existing cardiovascular disease, systolic blood pressure, serum albumin, TNF-α, and proteinuria were independently all associated with overhydration. Thus, volume overload is strongly associated with both traditional and novel risk factors for cardiovascular disease. Bioimpedance devices may aid in clinical assessment by helping to identify a high-risk group with volume overload among stages 3-5 CKD patients.

Vascular endothelial growth factor may provide additional values to C-reactive protein and anti-myeloperoxidase titer as a parameter for evaluating disease activity in anti-myeloperoxidase associated vasculitis.

Anti-myeloperoxidase (anti-MPO) associated vasculitis can result in rapid clinical deterioration. Immunosuppressive therapy is effective but involving considerable toxicity, and disease relapse frequently ensues. Laboratory parameters, such as C-reactive protein and anti-MPO titer, have substantial values in monitoring disease activity. However, the sensitivity and specificity are not satisfactory. This report presents the case of an old man with anti-MPO associated vasculitis. A parallel correlation between serum VEGF levels with C-reactive protein and anti-MPO titer was clearly demonstrated, implying a promising role of VEGF on monitoring disease activity in anti-MPO associated vasculitis. This is the first description of a correlation between VEGF and anti-MPO associated vasculitis.