Association of cardiac valve calcification and inflammation in patients on hemodialysis

BACKGROUND/AIMS: This study investigates the possible relationship between inflammation and cardiac valve calcification (VC) in patients on hemodialysis (HD), and identifies risk factors for VC in this patient group. METHODS: Seventy-nine patients on HD (mean age, 52.2 +/- 13.6 years; mean HD duration, 46.8 +/- 34.3 months) were assessed echocardiographically for the presence of VC. Systolic and diastolic blood pressure (BP) values were determined. The blood parameters studied in each case were hemoglobin, blood urea nitrogen, creatinine, calcium, phosphate, calcium-phosphorous (Ca x P) product, albumin, alkaline phosphatase, intact parathyroid hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride, lipoprotein(a), fibrinogen, and C-reactive protein (CRP). The number of patients receiving vitamin D and calcium-containing phosphate binder was determined from records, and presence of diabetes mellitus was noted. RESULTS: Cardiac VC was detected in 36 patients (46%). Five of these patients (6%) had mitral VC, 11 (14%) had aortic VC, and 20 (25%) had calcification of both valves. The patients with VC were significantly older than those without VC (60 +/- 11 vs. 43 +/- 15 years, respectively; P=.001). Compared with the group without VC, the group with calcification had significantly higher systolic (145.1 +/- 14.7 vs. 124.3 +/- 20.7 mmHg, P=.001) and diastolic BP (91.3 +/- 10.3 vs. 75.09 +/- 14.9 mmHg, P=.001); significantly higher phosphate (5.1 +/- 1.4 vs. 4.5 +/- 1.4 mg/dL, P=0.04), CaxP product (48.6 +/- 16.2 vs. 39.8 +/- 11.8, P=.01), lipoprotein(a) [28 (15, 45) vs. 16 (5,42) mg/dL, P=.04], fibrinogen (4.2 +/- 1.2 vs. 3.5-0.9, P=.005), and CRP levels [9 (4, 19) vs. 5 (3, 11) mg/L, P=.05]; and significantly longer HD duration [49 (27, 99) vs. 26 (17, 52) month, P=.01). Apart from age, duration of HD, systolic and diastolic BP, and Ca x P product, VC was associated with CRP (odds ratio, 1.151; P=.007) and fibrinogen (odds ratio, 1.119; P=.005). CONCLUSIONS: The results confirm well-known risk factors for cardiac VC in HD patients, such as older age, longer HD duration, elevated BP, and high Ca x P product. In addition, they suggest that elevated levels of CRP and fibrinogen were associated with VC in the HD population.     

Carotid atherosclerosis is associated with inflammation, malnutrition and intercellular adhesion molecule-1 in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Recent evidence suggests that endothelial cell adhesion molecules may participate in the initiation and progression of atherosclerotic vascular damage. The aim of the present report was to investigate serum intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin concentrations and their probable association with atherosclerotic disease in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Sixty-three CAPD patients and 40 age- and sex-matched apparently healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring the intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. RESULTS: Compared with controls, CAPD patients had significantly increased IMT and plaque score values (P<0.001 and P<0.0001, respectively), as well as serum ICAM-1, VCAM-1 and E-selectin concentrations (P<0.0001, P<0.0001 and P<0.05, respectively). In univariate analyses, IMT values were significantly correlated with age, systolic blood pressure (BP), logCRP, fibrinogen, albumin and ICAM-1 levels (P = 0.001, P = 0.04, P = 0.01, P = 0.04, P = 0.02 and P = 0.002, respectively). Multivariate analysis showed that ICAM-1 levels were a strong independent correlate of IMT (P = 0.005). Serum albumin also remained independently associated with IMT values (P = 0.03). Plaque score values were significantly correlated with age, systolic BP and fibrinogen (P = 0.002, P = 0.04 and P = 0.01, respectively). Multivariate analysis showed that fibrinogen concentrations were a significant independent contributor to plaque score values (P = 0.002). Adhesion molecule concentrations did not show any relation with plaque score either on univariate or multivariate analyses. CONCLUSIONS: In CAPD patients, carotid atherosclerosis is associated with markers of inflammation, malnutrition and circulating levels of adhesion molecule ICAM-1. Hypoalbuminaemia and ICAM-1 appear independently related with atherogenesis but the mechanisms supporting these associations remain to be identified.     

影响腹膜透析患者心脏瓣膜钙化与左房增大相关因素分析

目的 探讨腹膜透析患者心脏瓣膜钙化及左房增大的患病率与相关危险因素分析,为有效预防瓣膜钙化及左房增大的发生提供依据.方法 入选深圳市第二人民医院腹透中心稳定的接受规律持续性非卧床腹膜透析(CAPD)的患者,采集患者的人口统计学资料,测定血压,检测生化指标,评估患者的残肾功能和透析充分性,记录用药情况,使用心脏多普勒超声仪检测患者的心脏瓣膜钙化及左房内径情况.采用Logistic回归分析心脏瓣膜钙化和左房增大的危险因素.结果 71例患者入选本研究,男性38例(53.5％),女性33例(46.48％).所入选患者平均年龄(51.7±15.7)岁,平均透析龄(30.04±18.69)个月.其中28例(39.4％)患者存在心脏瓣膜钙化,31例(43.7％)患者存在左房增大.与无心脏瓣膜钙化患者相比,心脏瓣膜钙化患者的年龄(P=0.000)、左房内径(P=0.017)较大;尿素氮(P =0.028)、CTNI(P=0.005)、BNP(P=0.026)较高;总KT/V水平(P =0.007)较低.与左房内径正常的患者相比,左房增大患者的CTNI(P=0.009)、BNP(P =0.005)较高;铁蛋白(P =0.002)、总Ccr (P =0.041)较低.相关性分析表明,左房内径与年龄、CTNI、BNP、心脏瓣膜钙化呈正相关关系(P＜0.05);而血清总钙、铁蛋白、总Ccr呈负相关关系(P＜0.05).多因素Logistic回归分析结果显示年龄(OR=1.151,95％ CI:1.072～1.237,P=0.000),肌酐(OR=1.003,95％ CI:1.000 ～ 1.006,P=0.026)与这些患者发生瓣膜钙化独立正相关.尿素氮(OR=1.401,95％ CI:1.119～1.752,P=0.003),心脏瓣膜钙化(OR=21.149,95％ CI:1.737～ 257.459,P=0.017)与这些患者发生左房增大独立正相关;而尿酸(OR=0.982,95％ CI:0.967 ～ 0.997,P=0.017),视黄醇结合蛋白(OR =0.944,95％ CI:0.899 ～ 0.992,P=0.023),铁蛋白(OR=0.986,95％ CI:0.977 ～0.996,P=0.004)与左房增大独立负相关.结论 腹膜透析患者心脏瓣膜钙化和左房增大患病率较高.年龄、血清肌酐水平是心脏瓣膜钙化的独立危险因素,血清尿氮与心脏瓣膜钙化是左房增大的独立危险因素,血清视黄醇结合蛋白、血清尿酸、铁蛋白水平是左房增大的保护因素.左房增大与心脏瓣膜钙化互为因果,密切相关.     

Association between endothelial dysfunction and arterial stiffness in continuous ambulatory peritoneal dialysis patients

Objective To investigate the association between endothelial dysfunction and arterial stiffness in continuous ambulatory peritoneal dialysis （CAPD） patients. Methods Ninety-four stable CAPD patients from a single center were enrolled in this cross-sectional study. Ultrasound evaluation was conducted on brachial artery to estimate endothelial-dependent flow-mediated dilation (FMD). Automatice pulse wave velocity (PWV) measuring system was applied to examine the carotid-femoral PWV. Blood pressure and biochemical parameters were detected. Pearson's correlation and Stepwise multiple regression analysis were performed to explore the relationship between FMD and PWV. Results PWV was significantly higher in patients with diabetes as compared to those without diabetes[(13.25±1.66) m/s vs (11.24±1.92) m/s, P＜0.01]. Furthermore, PWV was positively correlated with age(r＝0.319, P＝0.002), SBP (r＝0.289, P＝0.005) and C-reactive protein (r＝0.211, P＝0.041), was negatively correlated with albumin (r＝-0.429, P＝0.001) and FMD (r＝-0.466, P＝0.001). In multivariate regression analysis, diabetes mellitus, albumin, FMD, age and SBP were independently associated with PWV after adjustment. Conclusion Endothelial dysfunction is associated with greater arterial stiffness in CAPD patients.     

Association between nutrition and peripheral artery disease in continuous ambulatory peritoneal dialysis patients

Objective To investigate the association between nutrition and peripheral artery disease (PAD) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods One hundred and two stable CAPD patients from a single center were enrolled in this cross-sectional study. Automatic ankle-brachial index (ABI) measuring system was applied to examine ABI. Patients were divided into PAD group (ABI＜0.9) and non-PAD group (ABI≥0.9). Clinical data were collected. Biochemical parameters were detected. Nutritional status was evaluated by serum albumin, handgrip strength (HGS) and subjective global assessment (SGA). Logistic regression analysis was performed to estimate the association of PAD with each nutritional marker as well as other potential risk factors. Results The incidence of PAD was 23.53% (24/102). ABI was significantly lower in patients with malnutrition as compared to those without malnutrition [(0.72±0.21) vs (1.04±0.14), P＜0.01]. Compared with non-PAD patients, serum albumin (P＜0.01), HGS (P＜0.01), diastolic blood pressure (P＜0.05), serum creatine (P＜0.05)、blood urine nitrogen (P＜0.01) were significantly decreased, but age (P＜0.01), the incidence of malnutrition [SGA, P＜0.01], diabetic status (P＜0.01), cardiovascular disease history (P＜0.01) were significantly increased in PAD patients. Logistic regression analysis showed that serum albumin (OR=0.762, 95％CI：0.611-0.948, P=0.015), HGS (OR=0.988, 95％CI：0.979-0.997, P=0.013) were independent protective factors for PAD, malnutrition [(SGA), OR=21.101, 95％CI：5.008-88.901, P＜0.01] was independent risk factor for PAD in CAPD patients. Conclusions The PAD incidence of CAPD patients in our center is 23.53%. Nutrition is independent factor associated with PAD in CAPD patients.     

Potassium metabolism in continuous ambulatory peritoneal dialysis patients

Background: Hypokalemia is common and may have contributed to the poor clinical outcome in peritoneal dialysis (PD) patients. In this study, we made a detailed investigation on the potassium metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients and tried to find out the possible factors associated with the high prevalence of hypokalemia in PD patients. Methods: A cross-sectional survey in 243 clinically stable CAPD patients was made in our PD center in 2010. Patients were divided into four groups according to whether they were anuric or not and different dialysis regimens. Patients’ demographic data and data on potassium metabolism including dietary potassium intakes, residual renal potassium, and peritoneal dialysis potassium removal were collected. Results: The average potassium intake in our 243 PD patients was 32.1?±?11.1?mmol/day. The total potassium removal was significantly higher in non-anuric patients as compared to anuric patients (33.2?±?9.1 vs. 23.0?±?4.7?mmol/day for 3 exchanges per day and 35.2?±?8.9 vs. 28.6?±?6.3?mmol/day for 4 exchanges per day, respectively, p?p?p?p?R² linear?=?0.645, p?Conclusions: Our study suggested that if potassium intake was limited in PD patients, we should be aware of the risk of hypokalemia with high doses of PD when patients have good RRF. Our study also suggested that potassium removal in PD patients may not necessarily reflect potassium intake even if serum potassium is normal, the effect of ICW should be considered when evaluating potassium homeostasis.     

Aspergillus peritonitis in continuous ambulatory peritoneal dialysis patients

Aspergillus peritonitis is a rare and serious cause of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We report 3 cases of aspergillus peritonitis in CAPD which were successfully treated by catheter removal and amphotericin. Two of the 3 patients returned temporarily to CAPD, but were subsequently transferred to hemodialysis because of membrane failure. A novel finding in 2 of the 3 cases was a positive Limulus amebocyte lysate test, despite negative bacterial cultures. We discuss the possible relevance of this finding to the diagnosis of aspergillus infections and emphasize the importance of early catheter removal for successful treatment of this condition.     

Inguinal herniation in two patients with continuous ambulatory peritoneal dialysis

We report two cases of subacute inguinal swelling in uremic patients on continuous ambulatory peritoneal dialysis (CAPD). Computed tomography, scintigraphy demonstrated a mass in the right groin. Surgical repair of an inguinal hernia resulted in complete resolution of the inguinal swelling. Both patients could restart continuous ambulatory peritoneal dialysis, without complication.     

Vancomycin pharmacokinetics in continuous ambulatory peritoneal dialysis patients with peritonitis

Peritonitis has proven to be the major deterrent to the further growth of continuous ambulatory peritoneal dialysis (CAPD) as a treatment strategy for end-stage renal disease. The correct treatment of peritonitis remains unsettled as evidenced by the presence of advocates for oral, intravenous or intraperitoneal antibiotic administration. This study examines the pharmacokinetic parameters of intravenous vancomycin when employed in the therapy of peritonitis. One gram of intravenous vancomycin was administered during 7 episodes of peritonitis in 5 patients. Plasma and end-of-dwell dialysate levels were maintained above the minimum inhibitory concentration for Staphylococcus aureus and S. epidermidis for 7 days following this single dose of vancomycin. These data establish the existence of sustained intraperitoneal entry of intravenous vancomycin during peritonitis and raise for speculation its use as the sole therapy in most episodes of gram-positive peritonitis.     

持续性非卧床腹膜透析患者容量超负荷与大动脉僵硬度的关系

目的探讨持续性非卧床腹膜透析（CAPD）患者细胞外液（ECW）与总体水（TBW）的比率（E／T）与脉搏波速度（PWV）的关系。方法选取56例CAPD患者为研究对象。自动PWV分析仪测定PWV。多频生物电阻抗分析仪对患者的容量状态进行评估。对相应指标进行相关及多元回归分析，筛选出PWV的影响因素。结果结果显示E／T（β=0．472．P=0．001）、脉压（β=0．442，P=0．001）、C反应蛋白（β=0．246，P=0．05）是PWV增加的独立危险因素。3者一起决定了PWV变化的58．1％，其中E／T决定37．8％。结论在透析患者中容量超负荷可能是通过动脉硬化程度的加重导致心血管疾病发生率和病死率增加的。     

Treatment of peritonitis in continuous ambulatory peritoneal dialysis patients with co-trimoxazole

Peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) represents the most frequent and difficult problem related to this new form of treatment of ESRD patients. Various treatments have been reported previously. The aim of this study was to investigate the efficiency of a standardized initial treatment in 45 episodes of peritonitis. This was designed to be rapidly efficient, devoided of side-effects and easy enough to be performed by the patients themselves. When peritonitis was clinically suspected, patients received intraperitoneal co-trimoxazole (80 mg trimethoprim, 400 mg sulfamethoxazole), in each of the four daily bags concomitantly with 1,000 U heparin during 2 weeks and half of this dose during 2 other weeks. Our results demonstrate that 88% of the isolates were sensitive to co-trimoxazole and 85% of the patients completed this treatment. All were cured and no relapses were observed. Only 18 days of hospitalisation were required in the 45 episodes of peritonitis. Another anti-infective agent was used in 3 cases of gram-negative peritonitis and 4 other initially resistant to co-trimoxazole. It is concluded that initial treatment of CAPD peritonitis with co-trimoxazole is justified by the high proportion of sensitive germs and that it represents a safe, efficient and inexpensive treatment.     

Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis

The aim of this study was to review the clinical features of tuberculous (TB) lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine cases of TB lymphadenitis were diagnosed among 910 patients over a period of 10 years. There were five men and four women with a mean age of 51 ± 15.5 years. The TB lymphadenitis involved the cervical lymph nodes in six patients, supraclavicular lymph nodes in two patients and mediastinal lymph nodes in one patient. Six patients presented with clinically enlarged lymph nodes of whom four also had fever. Three other patients were incidentally found to have enlarged lymph nodes on routine chest X-ray or ultrasound examination of the neck. Diagnosis of TB lymphadenitis was made by demonstrating caseating granulomata with or without positive acid-fast bacilli on excisional lymph node biopsy. All patients were cured with standard anti-tuberculosis drugs for 12 months. No recurrence of the TB lymphadenitis was observed after a mean follow-up of 59 ± 30 months. We conclude that TB lymphadenitis is not uncommon among patients on CAPD. A high index of suspicion is needed for early diagnosis of this condition. Prompt initiation of anti-tuberculosis treatment is associated with good prognosis.     

Ofloxacin pharmacokinetics in patients on continuous ambulatory peritoneal dialysis

Pharmacokinetics of ofloxacin (OFX) was studied in patients on continuous ambulatory peritoneal dialysis (CAPD) carrying out three exchanges per day. In 11 patients given 300 mg of OFX orally, serum OFX concentration peaked at 2.44 mg/l 3.7 hours after administration and the mean elimination half-life of OFX was 25 hours. OFX concentrations in peritoneal fluid underwent cyclical changes with each change of solutions, reaching beyond 0.5 mg/l after 2 hours of equilibration. There was a highly significant correlation between corresponding serum and peritoneal fluid concentrations of OFX after an 8 h equilibration (r = 0.85, p less than 0.001). In 5 patients given a 400 mg loading dose followed by 200 mg of OFX per day for 7 days, trough serum OFX concentrations ranged from 1.35 to 7.00 mg/l and no adverse effects were noticed. CAPD per exchange removed less than 2% of the total dose of OFX given.     

Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis

Albumin and protein removal rates were studied in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In nine patients simultaneous studies of albumin distribution and turnover were performed. Total albumin loss was 4.23 +/- 1.42 g/1.73 m2/24 hr; total protein removed was 8.79 +/- 4.21 g/1.73 m2/24 hr. Although these values were well within the range for severe nephrosis, serum albumin concentration remained nearly normal, 3.7 +/- 0.5 g/dl. Plasma albumin mass, 120.0 +/- 25.2 g/1.73 m2, and total albumin mass, 249 +/- 29.1 g/1.73 m2, did not differ from those of the control group. Compared with the control group, patients had reduced albumin catabolism, 9.76 +/- 1.74 g/1.73 m2/24 hr versus 13.8 +/- 0.77 g/1.73 m2/24 hr (P less than 0.001). Within the patient group albumin synthesis increased with increased albumin loss. Serum albumin concentration correlated negatively with albumin losses (P less than 0.001). The CAPD patients maintained albumin homeostasis through decreased albumin catabolism and increased synthesis. All major albumin pools were maintained despite massive albumin loss.     

Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients.

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.     

Protein losses in patients receiving continuous ambulatory peritoneal dialysis

Total protein and 12 specific proteins were measured in dialysates from 8 patients on continuous ambulatory peritoneal dialysis during training. Mean daily loss of total protein was 10.5 g and this included 5.2 g albumin, 805 mg of the immunoglobulins G, A and M, 323 mg transferrin and 530 mg of the remaining 7 proteins measured. The plasma to dialysate ratio of protein concentrations correlated with the natural logarithm of molecular weight, suggesting that proteins in dialysate are an ultrafiltrate of plasma. A greater loss of proteins overnight was due to longer dwell time as the mean rate of loss was similar for all exchanges. Losses were similar with 1.36% and 3.86% dextrose fluids, suggesting that the initial effects of hypertonicity are diminished or reversed by dilution and absorption of dextrose. Daily outflow volumes for 4 patients correlated inversely with the quantities of several proteins removed, probably due to effects of osmolality. It is concluded that protein losses are related to plasma concentration, molecular weight and osmolality of the dialysis solution and to the physiology of the patient.     

Procainamide pharmacokinetics in patients on continuous ambulatory peritoneal dialysis

The pharmacokinetics of procainamide in patients on continuous ambulatory peritoneal dialysis have been studied. A mean peak plasma concentration of 3.2 +/- 0.6 microgram/ml was achieved about 2 h after a single 500-mg oral procainamide hydrochloride dose. The procainamide elimination half-life ranged from 6.1 to 15.3 h. Apparent oral clearance, 183.7 +/- 63.2 ml/min, was less than half that observed in healthy adults suggesting markedly reduced dosage requirements. Continuous ambulatory dialysis patients exhibit similar procainamide pharmacokinetic parameters as do end stage renal disease patients, most notably a prolonged elimination half-life and reduced oral clearance.