Self-perceived symptoms and care needs of patients with severe to very severe chronic obstructive pulmonary disease,congestive heart failure or chronic renal failure and its consequences for their closest relatives: the research protocol

Background  

Recent research shows that the prevalence of patients with very severe chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and chronic renal failure (CRF) continues to rise over the next years. Scientific studies concerning self-perceived symptoms and care needs in patients with severe to very severe COPD, CHF and CRF are scarce.     

慢性心力衰竭合并慢性肾炎患者尿液中B型尿钠肽水平与心功能的相关性研究

目的：探讨慢性心力衰竭(chronic heart failure,CHF)合并慢性肾炎患者尿液中血清B型钠尿肽(B-natriuretic peptide,BNP)水平与心功能的相关性。方法：选取2013年6月至2015年6月在我院接受治疗的慢性心力衰竭患者为观察对象,根据其是否合并慢性肾炎分为CHF组和CHF合并慢性肾炎组。观察两组患者肾功能指标及尿BNP水平,比较两组患者心功能指标的差异,分析肾功能指标、尿BNP与心功能的相关性。结果：CHF合并慢性肾炎组患者尿素氮(blood urea nitrogen, BUN)、血清肌酐(serum creatinine,SCr)和BNP水平明显高于CHF组,而肾小球滤过率(glomerular filtration rate,GFR)水平明显低于CHF组,差异具有统计学意义(P<0.05);CHF合并慢性肾炎组患者左心房直径(left atrial diameter,LAD)、右心房直径(right atrial diameter,RAD)、左室收缩末内径((left ventricular end systolic diameter,LVESD)和左室舒张末内径(left ventricular end diastolic diameter,LVEDD)水平明显高于CHF组患者,左室射血分数(left ventricular ejection fractions, LVEF)水平明显低于CHF组,差异具有统计学意义(P<0.05);CHF合并慢性肾炎患者的BUN、SCr、BNP与LAD、RAD、LVESD和LVEDD正相关,与LVEF负相关,GER水平与LAD、RAD、LVESD和LVEDD负相关,与LVEF正相关。结论：慢性心力衰竭合并慢性肾炎患者尿液BNP水平较高,且与患者的心功能指标密切相关,可作为临床监测指标。     

Renal osteodystrophy in predialysis patients without stainable bone aluminum. A cross-sectional bone-histomorphometric study

Histomorphometry was performed on transiliac bone biopsies, double-labeled with tetracycline, from 60 consecutively admitted patients (20 women) at various stages of chronic renal failure (CRF). Eleven patients (1 woman) had normal bone resorption and formation indices. Bone resorption and osteoid formation increased with progression of renal failure, but abnormal values were seen even at slightly elevated creatinine levels. Mineralization lag time increased with CRF duration; prolonged values were only seen in patients with polycystic kidney disease or chronic pyelonephritis with advanced CRF. All patients with impaired mineralization also had increased bone resorption. Diabetes mellitus did not protect against skeletal lesions. The biochemical tests were too insensitive to predict type or severity of bone disease, and hand X-rays had no diagnostic value in early stages of renal osteodystrophy.     

精氨酸加压素对慢性肾衰大鼠心功能及其心肌细胞钠-钾-ATP酶活力的影响

用SD大鼠制作慢性肾衰(CRF)动物模型,观察其血浆与心肌精氨酸加压素(AVP)含量的变化;CRF大鼠静脉分别注射AVP及其抗血清,观察其对平均动脉压、左心室压峰值和心肌细胞钠-钾-ATP酶(Na~+,K~+-ATP酶)活力的影响。结果表明,CRF~+大鼠血浆及心肌AVP含量与血肌酐水平同步增高;静脉注射AVP标准品,可使心肌Na~+,K~+-ATP酶活力明显降低,并加重心功能指标的异常变化;而给予AVP抗血清,则可改善心功能,对心肌有明显的保护作用。提示ATP含量异常增高所引起的Na~+,K~+-ATP酶泵转运动力学损害,可能参与CRF时心功能不全的病理过程。     

Chronic renal failure after heart, lung, liver, or intestine transplantation

Acute and especially chronic renal failure (CRF) are relatively common and important risk factor for morbidity and mortality in patients after heart, lung, liver or intestine transplantation. Numerous factors contribute to the development of CRF in this group of patients, like treatment with calcineurin inhibitors and other nephrotoxic drugs in the perioperative period, hemodynamical changes during and after the surgery, preexistent renal disease, hypertension, diabetes mellitus, dyslipidemia and anemia. Pretransplant evaluation of renal function is mandatory to predict which patients have increased risk for development of CRF. In the posttransplantation course it is necessary to timely diagnose and treat renal failure, while patients with insufficient renal function have 4.55-fold increased risk of death compared to patients with normal renal function. Special problem is diagnostic approach to patients with suspected chronic renal disease who are candidates for transplantation of other parenhimatose organs. Diagnostic value of serum creatinine and estimation of renal function based on its value is very limited. Gold diagnostic standard is radioisotope estimation of glomerular filtration, but this method is not widely available. It seems that this problem may be solved with the use of cystatin C, but this approach needs to be validated in large studies. Numerous different immunosuppressive drugs available on the market enable individualization of immunosuppression. Different drugs combinations may have less nephrotoxic potential, but one must be careful because of the possible risk of organ rejection with the change of immunosuppression. Use of angiotensin convertase enzyme inhibitors and/or angiotensin receptor blockers, statins with drugs for control of hyperglycemia, may prevent or postpone development of CRF. Although technical advances of contemporary hemodialysis machines and peritoneal dialysis equipment enable well tolerated dialysis even in critically ill patients, renal transplantation remains the method of choice for treatment of patients with transplanted parenhimatous organ that developed CRF.     

Reduced thickness of gastric mucosa and retarded progression of chronic gastritis in patients with renal failure

Conflicting results are reported in the literature on the structure and function of gastric mucosa in patients with chronic renal failure (CRF). In the present endoscopic study of 68 CRF patients on conservative treatment (regular dialyses or transplantations had not yet been undertaken), we sought to clarify whether CRF leads to hypertrophic or hypotrophic phenomena in gastric mucosa, as interpreted by the presence and grade of gastritis and by the thickness of the gastric mucosa. We found that the mean progression of gastritis in both antrum and body was significantly slower than expected in CFR patients, and that the thickness of both antral and body mucosa was significantly lower in CFR patients than in non-CRF controls. Furthermore, although the thickness of the oxyntic body mucosa in CRF showed a positive correlation to serum gastrin (SeGa) levels and even though 12 of the patients showed high SeGa levels corresponding to those seen in the Zollinger-Ellison synbdrome (300-1500 ng/l), the thickness of the oxyntic body mucosa in CRF patients did not exceed that seen in control subjects with normal SeGa. We conclude that CRF exerts inhibitory effects on the gastric mucosa resulting in retardation in the progression of chronic gastritis and hypotrophy of the gastric mucous membrane.     

Prevalence and patterns of left ventricular hypertrophy in patients with predialysis chronic renal failure.

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac death. This study evaluates the prevalence and patterns of LVH in patients with predialysis chronic renal failure (CRF) and analyses the relationship between LVH and various predisposing factors. Sixty-two CRF patients were recruited from the renal clinic with serum creatinine over 2 mg/dl. Using echocardiography, we calculated the left ventricular mass index (LVMI) and relative wall thickness (RWT), and classified the patients into four groups (Group 1: normal, Group 2: concentric remodelling, Group 3: concentric hypertrophy, Group 4: eccentric hypertrophy). Prevalence and patterns of LVH in patients with CRF were as follows; 6.5% in Groups 1 and 2, 56.5% in Group 3 and 30.5% in Group 4. LVMI increases with progressive renal function decline. There were linear correlations between LVMI and systolic and diastolic blood pressure (BP), serum creatinine (Scr) and intact parathyroid hormone (PTH) in patients with predialysis CRF and also inverse linear correlations between LVMI and creatinine clearance (Ccr) and hemoglobin. In conclusion, we demonstrate the high prevalence of LVH (87%) in patients with predialysis CRF and concentric hypertrophy (56.5%) was the main pattern of LVH. Several factors such as anemia, systolic and diastolic BP, renal function and PTH influence LVMI.     

Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Graphical Abstract

相似文献   

The cardiorenal link in advanced cirrhosis

A considerable number of patients with advanced cirrhosis develop a hepatorenal syndrome. The pathogenesis involves liver dysfunction, splanchnic vasodilatation, and activation of vasoconstrictive systems. There are now several observations that indicate a relation between the renal failure and impaired cardiac function in patients with advanced cirrhosis. Cirrhotic cardiomyopathy has been described as a condition with impaired contractile responsiveness to stress and altered diastolic relaxation. We propose a cardiorenal interaction in patients with advanced cirrhosis and renal dysfunction that refers to a condition where cardiac dysfunction in cirrhosis is a major determinant of kidney function and survival. Thus, the relation between cardiac dysfunction and renal insufficiency should be target for future studies and development of new treatments should focus on ameliorating the cardiac dysfunction.     

Disturbance of the autonomic nerve system in patients with chronic renal failure--represented by variation coefficient of R-R intervals in the ECG as a parameter

Autonomic nerve dysfunction in patients with chronic renal failure has of late become an issue to be investigated. R-R intervals in resting electrocardiograms were measured to evaluate activities of the cardiac parasympathetic nerve system. A total of 140 patients with chronic renal failure were studied to be compared with 20 normal controls (cont.) and 39 with diabetes mellitus (DM). Of these patients 15 were subjected to conservative treatment (CRF), while 125 patients were undergoing hemodialysis due to chronic renal failure-100 of them derived from chronic glomerulonephritis (HD) and 25 from diabetes mellitus (DM.HD). The variation coefficient of the R-R interval (CVRR) was measured after the subject patients had rested for over 15 minutes before a dialysis session. The mean CVRR were 2.15 +/- 1.25% in CRF group, 2.36 +/- 1.37% in HD and 1.37 +/- 0.99% in DM.HD. These values were significantly lower than in control group (4.70 +/- 2.64%). On the other hand, the value in DM.HD group, as shown above, was significantly lower than in HD. In CRF group the CVRR values lowered as residual renal functions decreased. No significant correlations between CVRR S and the duration of hemodialysis treatment were noted among the groups. In HD group the CVRR S were significantly lower in patients with hypotensive tendency during hemodialysis than in those who enjoyed good control of blood pressure. These results suggest that the measurement of CVRR S can be of help in evaluating autonomic nerve dysfunction in patients with chronic renal failure.     

慢性肾衰患者外周血IL-18水平及血液透析对其的影响

为探讨慢性肾衰竭 (CRF )患者外周血IL 18表达量的变化以及血液透析 (HD )对其表达的影响 ,选取 10名健康志愿者及 2 9例CRF患者 ,应用ELISA测定血浆IL 18水平 ,同时采用半定量逆转录多聚酶链反应 (RT PCR )技术 ,检测PBMC中IL 18mRNA表达量。结果是未行HD的CRF患者血浆IL 18水平及PBMCIL 18mRNA表达量较正常对照组增高 ,差异有显著统计学意义 (P <0 0 1) ,单次HD对CRF患者血浆IL 18水平及基因表达无明显影响 (P >0 0 5 ) ,但长期维持HD则可使CRF患者外周血IL 18水平及基因表达增高 (P <0 0 5 )。提示外周血IL 18的高表达可能参与CRF的发病过程及HD相关并发症的发生发展     

Clinical Potential of Growth Hormone in the Treatment of Congestive Heart Failure

Substantial evidence supports a role for the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis in regulation of normal cardiac growth, structure and function. Moreover, experimental data suggest beneficial effects of GH and IGF-1 on contractility and peripheral resistance in rats with impaired cardiac function. An increased Ca(++) responsiveness is one possible underlying cause for the improvement in contractility, although effects of GH and IGF-1 on apoptosis may also play a more long term role for cardiomyocyte survival. Until recently, studies regarding GH treatment in heart failure were limited to case reports where administration dramatically improved cardiac function. In a small non-blind study of 7 patients with idiopathic dilated cardiomyopathy and congestive heart failure (CHF) without GH deficiency who received treatment with recombinant GH (somatropin) for 3 months, considerable improvement of cardiac function was reported. More recent studies have demonstrated beneficial effects in patients with CHF due to both ischaemic and idiopathic dilated cardiomyopathy, with improvements in haemodynamics when somatropin was added both as a maintenance therapy and as a short term infusion. So far, 2 placebo-controlled studies with somatropin as adjunctive therapy in patients with CHF have been reported, although neither study could confirm previously reported improvement in systolic function and lowering of wall stress. In summary, it is clear that further placebo-controlled clinical trials are mandatory to verify positive effects and to monitor long term safety when somatropin is administered as an agent in the treatment of CHF.     

慢性心衰大鼠下丘脑室旁核瞬时外向钾通道蛋白Kv4.2和Kv4.3低表达促进肾交感神经兴奋性

 目的: 观察慢性心衰大鼠下丘脑室旁核内瞬时外向钾通道蛋白Kv4.2和Kv4.3的变化及其对交感神经活性的影响。方法: 采用冠状动脉左前降支结扎术建立大鼠心衰模型或假手术模型,造模4周后超声心动图测定心功能;酶联免疫吸附法测定血浆去甲肾上腺素(NE)及血清N端前脑钠肽(NT-proBNP)含量;Western blot和real-time PCR法测定室旁核内Kv4.2和Kv4.3的表达情况;室旁核部位注射钾通道阻滞剂4-氨基吡啶(4-AP),电生理记录仪记录血压、心率和肾交感神经放电的变化。结果: 与假手术组比,心衰组大鼠心功能明显降低,血浆NE及血清NT-proBNP明显升高,室旁核内Kv4.2和Kv4.3表达明显下调;注射4-AP后导致血压、心率和交感神经放电升高,但心衰组的升高幅度小于假手术组。结论: 心力衰竭时室旁核内Kv4.2和Kv4.3表达下调并伴有交感神经放电增加,促进心衰进展。     

交感神经皮肤反应对评价慢性肾功能不全患者植物神经损害的意义

目的:探讨慢性肾功能不全(CRF)患者交感神经皮肤反应(SSR)的变化及其临床意义。方法:对52例CRF患者行SSR检测,并与32例正常对照组比较。结果:CRF组SSR波幅低于正常对照组,潜伏期较对照组延长(P<0.01)。CRF组SSR总异常率为71%,其中上肢异常率为48%,下肢异常率为71%;慢性肾衰早期组16例中7例(44%)SSR异常,慢性肾衰组19例中14例(74%)SSR异常,尿毒症组17例中16例(94%)SSR异常;CRF患者上下肢之间、不同亚组之间SSR异常率比较差异有极显著意义(P<0.01)。CRF组病程和血肌酐水平与SSR潜伏期间的偏相关系数分别为0.4732(P<0.01)和0.3247(P<0.05),而与SSR波幅间的偏相关系数为-0.3173和-0.3062(P均<0.05);年龄与SSR潜伏期偏相关系数为0.0434(P>0.05),与SSR波幅偏相关系数为-0.4445(P<0.01)。结论:SSR的异常反映了CRF患者常合并交感神经损害,且与病程、肾功能损害程度及年龄因素相关,SSR检测可作为评价CRF患者交感神经损害敏感的客观指标。     

Urinary indoxyl sulfate is a clinical factor that affects the progression of renal failure

We recently demonstrated that indoxyl sulfate is a stimulating factor for the progression of chronic renal failure (CRF). In this study we determined whether the urine or serum levels of indoxyl sulfate are related to the progression rate of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120) were randomly enrolled in the study. We measured the serum and urine levels of indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl sulfate urine levels of >60 mg/day had a significantly faster progression rate of CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate urine levels of >90 mg/day had the highest CRF progression rate and those with indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate. Urinary indoxyl sulfate had a significantly negative correlation with the slope of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio of serum indoxyl sulfate to creatinine was not significantly correlated with the slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl sulfate are related with a rapid progression of CRF in undialyzed uremic patients. Thus, urinary indoxyl sulfate is one of the clinical factors that affect CRF progression.     

Optimal Use of Epoetin-α in the Anaemia of Chronic Renal Failure

Anaemia, a major feature of chronic renal failure, is responsible for a significant proportion of the multisystemic disabling symptoms in patients with chronic renal failure (CRF). Anaemia correction with recombinant human erythropoietin (epoetin-alpha) often leads to significant amelioration of these symptoms. Starting dose should be 50 U/kg of bodyweight given subcutaneously or intravenously 1, 2 or 3 times a week. The subcutaneous route is more effective, resulting in use of less epoetin-alpha and subsequent cost-saving. Adverse effects of epoetin-alpha tend to be more severe and more likely following intravenous administration. Once the target haematocrit is achieved, the epoetin-alpha dose should be reduced by 50 to 80%, but should not be stopped, since an abrupt fall in haematocrit may ensue if epoetin-alpha is completely discontinued. There is an emerging consensus that it is deleterious, and not necessary, to allow patients to become severely anaemic before starting epoetin-alpha. Thus, the current trend is to start epoetin-alpha once the haematocrit is 30 to 35%. On the other hand, what the target haematocrit should be is controversial. The threshold haematocrit beyond which the risks of anaemia correction outweigh the benefits in patients with CRF is not established. Studies that assessed quality of life outcomes as well as clinical experience in Europe clearly demonstrate better outcomes without adverse effects in patients with a haematocrit between 36 to 40%, compared to those with haematocrit of 30%. Prior to starting epoetin-alpha in any patient with CRF, a methodological evalution should be performed to exclude other major causes of anaemia and to identify any comorbid conditions that may impair response to epoetin-alpha. Response to epoetin-alpha may be impaired by loss of residual renal function in patients with progressive CRF or kidney transplant recipients. Other major factors that impair response to epoetin-alpha include impaired utilisation of iron, absolute iron deficiency, inadequate dialysis, infection and bone marrow fibrosis.     

慢性肾功能衰竭患者血浆同型半胱氨酸及血脂水平变化

目的 :了解慢性肾功能衰竭 (CRF)患者血浆中同型半胱氨酸(Hcy)和血脂水平的变化和透析治疗CRF前后血浆中Hcy水平的变化。方法 :以微板底物诱导法测定CRF患者、冠心病 (CHD)患者和健康者血浆中Hcy和其它血脂指标的浓度 ,并讨论与分析。 结果 :CRF患者血浆Hcy水平明显高于正常组 (P <0 .0 5 )。透析治疗观察发现CRF患者血液透析后 2hHcy水平较透析前下降 45 .7% ,透析后 2 4hHcy水平较透析前仅下降 8.9%。CRF患者血清Hcy和TG之间存在正相关性 (r =0 .719)。结论 :CRF患者普遍存在高Hcy血症 ,动态观察患者血脂、Hcy和肾功能水平 ,对了解病情进展和治疗效果有积极作用     

The role of mesenchymal stem cells in the functional improvement of chronic renal failure

The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF). Sprague-Dawley female rats (8 weeks old, 182.2 +/- 7.2 g) underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 x 10(6) cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-h urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients. No significant differences in blood urea nitrogen and creatinine concentration were observed between the MSC group and the untreated CRF group. However, the weight gain in the MSC group was greater than those in the CRF group after 4 months. Proteinuria in the MSC group was less than that in the CRF group over time. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between these two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis. These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.     

下丘脑室旁核小电导钙激活钾通道过表达降低慢性心衰大鼠肾交感神经兴奋性

 目的：研究下丘脑室旁核小电导钙激活钾通道亚型2（SK2）过表达对慢性心衰大鼠心率、血压和肾交感神经活性的影响,揭示心衰大鼠下丘脑室旁核对交感系统的调节机制。方法：构建SK2重组腺病毒穿梭载体pDC316-mCMV-EGFP-rKCNN2。采用SD大鼠,手术组用左冠状动脉前降支结扎术制作慢性心衰模型,假手术组大鼠左冠状动脉前降支下穿线但不结扎,术后6周用超声心动图测定心功能。心衰组和假手术组分别在室旁核微量注射 SK2 腺病毒pDC316-mCMV-EGFP-rKCNN2和对照腺病毒pDC316-mCMV-EGFP,7 d后通过超声心动图检测心功能的改变;运用免疫组织化学、RT-PCR和Western blotting方法检测SK2重组腺病毒转染情况及表达。室旁核微量注射SK通道阻滞剂apamin,通过PowerLab 8/30系统采集信号记录心率、血压和肾交感神经活性的变化。结果: 心衰大鼠SK2表达较假手术组减少,下丘脑室旁核微量注射SK2腺病毒导致心衰大鼠肾交感神经兴奋性明显降低,下丘脑室旁核微量注射对照腺病毒对假手术大鼠交感神经兴奋性的改变不明显。结论：SK通道蛋白在心衰状态下表达降低并可能导致其功能减弱,进而促成由SK2通道介导的中枢负性交感调节通路的降低,增加了交感神经兴奋性,从而加重心衰的发展。SK2过表达减弱了心衰大鼠的肾交感神经活性,为治疗心衰提供了新的方向。     

血浆白细胞介素-18水平在慢性心力衰竭患者中的应用价值

目的 探讨白细胞介素-18(interleukin-18,IL-18)水平在慢性心力衰竭(CHF)诊断中的应用价值.方法 选取2014年1月至2015年6月就诊的97例CHF患者为研究对象,依据美国纽约心脏病学会(NYHA)心脏功能分级标准,分为Ⅱ级(31例)、Ⅲ级(30例)和Ⅳ级(36例),并选择35例同期体检的健康人群为对照组.空腹采集肘静脉血,应用酶联免疫法检测IL-18水平.结果 CHF各组患者血浆IL-18水平与对照组比较,差异有统计学意义(P＜0.05).随着病情的进展,血浆IL-18水平呈显著升高趋势(P＜0.05).结论 IL-18用于评价慢性心力衰竭有一定的临床价值.