慢性肾衰竭患者代谢性酸中毒与营养不良-炎症反应综合征

代谢性酸中毒(MA)是慢性肾衰竭患者常出现的临床表现,可能与蛋白质-热能营养不良(PEM)和炎症有关,后两者合称为营养不良-炎症反应综合征(MICS).酸血症是引起慢性肾衰竭患者预后不良和死亡的重要原因.然而新近许多流行病学的研究显示慢性肾衰竭患者MA的"逆流行病学"现象.本文就MA与慢性肾衰竭患者MICS关系的研究进展作一综述.     

Interrelationship between plasma leptin concentration and severity of metabolic acidosis in haemodialysed patients with chronical renal failure.

Patients with chronic renal failure are frequently characterized by malnutrition, hyperleptinaemia and metabolic acidosis. Both hyperleptinaemia and chronic metabolic acidosis are presumed to contribute to the pathogenesis of malnutrition observed in this group of patients. It has been reported, that in vitro adipocytes exposed to acidotic medium decrease leptin secretion. The aim of present study was to analyze the possible impact of uraemic metabolic acidosis on leptinaemia in haemodialysis patients with chronic renal failure. - 94 haemodialysed patients (58 M, 36 F; mean age 45 +/- 1 years) were enrolled in this study. 56 patients were on haemodialysis treatment for one year using an acetate dialysis fluid, while 38 patients were haemodialysed at least for 3 months with a dialysate buffered with bicarbonate. Plasma leptin concentration, blood gases and body composition were assessed in all examined subjects. - Patients haemodialysed with an acetate and bicarbonate buffered dialysate did not differ with respect to body weight, body mass index (BMI), total fat mass (TFM) and plasma leptin concentration. Patients haemodialysed with an acetate buffered dialysate were characterized by a significantly more severe metabolic acidosis than patients on bicarbonate haemodialysis. Patients were divided according to the actual hydrogen ion concentration: over 60 nmol/l, 45-60 nmol/l and below 45 nmol/l. These subgroups did not differ significantly by body weight, BMI and TFM. Only a slightly (not significantly), lower median leptinaemia was found in patients with elevated hydrogen ion concentration. No significant correlation was noticed between blood hydrogen or hydrocarbonate ion concentration respectively and logarithmic values of plasma leptin concentration (tau = 0.025, p = 0.72; tau = - 0.021, p = 0.76 respectively). - From results obtained in this study we may conclude that, blood hydrogen ion concentration does not influence substantially or only moderately to plasma leptin concentration in haemodialysed patients.     

Sulfatides are required for renal adaptation to chronic metabolic acidosis

Urinary ammonium excretion by the kidney is essential for renal excretion of sufficient amounts of protons and to maintain stable blood pH. Ammonium secretion by the collecting duct epithelia accounts for the majority of urinary ammonium; it is driven by an interstitium-to-lumen NH₃ gradient due to the accumulation of ammonium in the medullary and papillary interstitium. Here, we demonstrate that sulfatides, highly charged anionic glycosphingolipids, are important for maintaining high papillary ammonium concentration and increased urinary acid elimination during metabolic acidosis. We disrupted sulfatide synthesis by a genetic approach along the entire renal tubule. Renal sulfatide-deficient mice had lower urinary pH accompanied by lower ammonium excretion. Upon acid diet, they showed impaired ammonuria, decreased ammonium accumulation in the papilla, and chronic hyperchloremic metabolic acidosis. Expression levels of ammoniagenic enzymes and Na⁺-K⁺/NH₄⁺-2Cl⁻ cotransporter 2 were higher, and transepithelial NH₃ transport, examined by in vitro microperfusion of cortical and outer medullary collecting ducts, was unaffected in mutant mice. We therefore suggest that sulfatides act as counterions for interstitial ammonium facilitating its retention in the papilla. This study points to a seminal role of sulfatides in renal ammonium handling, urinary acidification, and acid–base homeostasis.Low blood pH, as it occurs in metabolic acidosis, affects cellular functions and can lead to increased morbidity and mortality (1). The mammalian kidney plays a central role in the regulation of extracellular osmolality and fluid volume as well as the maintenance of blood pH in a narrow range of pH 7.35–7.45 (2). Excess protons are buffered by bicarbonate synthesized during renal ammoniagenesis and excreted into urine mainly bound to NH₄⁺ (ammonium) and titratable acids. During metabolic acidosis, enhanced ammonium excretion accounts for more than 80% of the increase in urinary net acid excretion in humans and rodents (3, 4). Ammonium (NH₃ and NH₄⁺) is produced in proximal tubular (PT) epithelia, secreted into the PT lumen, and is largely reabsorbed in the thick ascending limb of Henle’s loop (TAL). This process results in high interstitial ammonium concentrations in the medulla and the papilla and thereby, in parallel to the gradient of hypertonicity, in a cortico-papillary ammonium gradient facilitating secretion of ammonium into medullary collecting ducts (4). Several transport proteins have been shown to mediate medullary TAL NH₄⁺ reabsorption (5). However, the mechanisms that underlie the maintenance of high interstitial NH₄⁺ concentrations in the medulla and papilla, thereby avoiding backflux into the systemic circulation, have remained unexplored.Sulfatides are a subclass of anionic glycosphingolipids (GSLs), which consist of ceramide and carbohydrate residues to which one or several sulfate esters are bound via enzymatic catalysis by cerebroside sulfotransferases (CST; Cst). In mammals, sulfatides accumulate in the kidney with particularly high concentrations in the distal nephron segments and the renal medulla (6). The major renal sulfatide in humans and rodents is the galactosylceramide (GalCer)-derived SM4s. Other sulfated GSL species such as the glucosylceramide (GlcCer)-derived SM3 (sulfated lactosylceramide) in humans and mice and SB1a (gangliotetraosylceramide-bis-sulfate) in mice are even more polar than SM4s (7) (Fig. 1A).Fig. 1.Pax8-driven deletion of renal neutral and sulfated GSLs. (A) Ugcg- and Cst-dependent synthesis of neutral and acidic GSLs in the mouse kidney. (B) Cloning strategy for the disruption of the Cst gene. Disruption of the Ugcg gene has been described previously ...Various kidney diseases such as renal cell carcinoma and polycystic kidney disease are associated with disturbances in renal sulfatide metabolism (8, 9). However, the basic physiological function of renal sulfatides is not known. They are mainly found in the outer part of the plasma membrane. Apart from mediating cellular interactions with various external ligands, e.g., l-selectin, the anionic charge carried by sulfatides on the membrane surface may point to a modulatory role in membrane ion fluxes and/or binding of cationic extracellular substrates (7, 10, 11). Sulfatides at the cell membrane were surmised to function as ion barriers to extracellular osmolality oscillation (12, 13). Furthermore, they have been discussed to act as cofactors of basolateral Na⁺-K⁺-ATPase activity by binding K⁺ or by facilitating the membrane relocalization of the enzyme (14–16). Zalc et al. (17) have proposed a role of sulfatides rather in passive sodium chloride diffusion in the TAL.However, renal abnormalities have not been reported either in mice with systemic disruption of UDP-galactose:ceramide galactosyltransferase (Cgt; CGT) lacking SM4s or in Cst^−/− mice with deficiency of all sulfatides most probably due to the dominant and finally lethal central nervous system phenotypes (18, 19).The aim of this study was to assess in vivo the hypothesis that sulfatides are involved in ion transport processes in the kidney by a combined molecular genetic and physiological approach. Therefore, we have generated mice with disruption of the Cst gene and UDP-glucose:ceramide glucosyltransferase (Ugcg) gene and combinations of both in a tubular epithelial cell-specific manner under control of the paired box gene 8 (Pax8) promoter (20). This approach was taken to reduce the possibility for compensatory synthesis of charged GSLs as well as to circumvent systemic effects (18, 21, 22). Here, we show that sulfatides, most probably by their anionic extracellular charge, are required to maintain high interstitial ammonium concentration in the papilla, which is needed for appropriate ammonium excretion into urine under basal conditions and during metabolic acidosis.     

在常规治疗基础上应用卡维地洛治疗慢性心力衰竭并发肾功能不全患者的效果

目的观察在常规治疗基础上应用卡维地洛对慢性心力衰竭（CHF）并发肾功能不全患者的临床疗效。方法采用自身对照的方法,27例CHF并发肾功能不全的患者在接受常规治疗的基础上加用卡维地洛直到目标剂量,比较治疗前及治疗12周后患者的心功能和肾功能。结果治疗12周后患者左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）较治疗前明显缩小（P<0.01）,左室射血分数（LVEF）较治疗前显著增高（P<0.01）。治疗12周后血尿素氮（BUN）、肌酐（Cr）、β2-微球蛋白（β2-MG）较治疗前明显降低（P<0.01）。结论在常规治疗基础上应用卡维地洛能明显改善CHF并发肾功能不全患者的心功能和肾功能。     

老年人慢性心力衰竭治疗进展

慢性心力衰竭（chronic heart failure,CHF）是备受关注的全球公共卫生问题,我国心力衰竭（心衰）流行病学调查结果显示：年龄〉60岁的老年慢性心衰患者占50%以上,并且,80%的住院心衰患者〉60岁。美国Framingham研究也显示：     

Surgical infections in patients with chronic renal failure

Patients with chronic renal failure and uremia have impaired host defenses and wound healing that can lead to an increased risk of infection in addition to a frequent need for surgical procedures with synthetic grafts and catheters. Antibiotic therapy plus timely surgical intervention in removal of infected grafts and catheters is crucial for infection control and patient survival. Other surgical infections, such as wound problems, intraabdominal infections, fungal infections, diabetic foot ulcers, and necrotizing soft tissue infections must be attended to promptly.     

Hyperhomocysteinemia in patients with mild chronic renal failure

BACKGROUND: The aim of this study was to evaluate the prevalence of high plasma levels of homocysteine in patients with mild renal failure. METHODS: Forty-six chronic renal failure patients (25 males and 21 females, mean age 55.6+/-14.4 years) were recruited for the study. Mean plasma creatinine was 2.1+/-1.0 mg/dl and mean creatinine clearance was 50.6+/-26.3 ml/min. Patients with severe renal failure were excluded. Patients were compared with a control group with normal renal function (n=35, 22 men and 13 women, mean age 50.0+/-11.5 years). Plasma homocysteine values were measured in both groups at baseline and after an oral overload of methionine. RESULTS: Baseline homocysteine levels of patients were higher than those of controls (16.5+/-7.3 vs. 10.4+/-4.2 micromol/l, p<0.0001). Some 34 patients and 4 controls had increased plasma homocysteine levels at baseline. After the oral overload, 4 more patients had abnormally increased homocysteine levels, meaning that 83% of the patients with chronic renal failure had hyperhomocysteinemia. CONCLUSIONS: Hyperhomocysteinemia is a very common finding among patients with mild renal failure. The need for vitamin supplementation should be evaluated in the first stage of chronic renal failure.     

Pulmonary hypertension in patients with chronic renal failure

BACKGROUND: Many etiologies causing pulmonary hypertension (PH) have been reported, and one of the background disease seen with patients with PH is chronic renal failure (CRF); however, the pathogenesis of PH in this group of patients is not explained satisfactorily. OBJECTIVES: The aims of this study were to evaluate the incidence of unexplained PH among patients with CRF and to suggest possible etiologic factors. METHODS: Two hundred and eleven patients with CRF were evaluated and the ones who have comorbid conditions that cause PH were excluded. Pulmonary arterial pressure (PAP) and cardiac functions were evaluated by Doppler echocardiography. Arteriovenous fistula (AVF) flow was measured by Doppler sonography. The patients were followed for at least 6 months. RESULTS: Forty-eight CRF patients (20 males, 28 females) were included: 23 were predialysis patients, and 25 patients received hemodialysis via AVF. Patients were followed for 7.5 +/- 1.01 months. Systolic PAP >35 mm Hg was found in 56% (14/25) of patients receiving hemodialysis (36.8 +/- 10.7 mm Hg) and in 39.1% (9/23) of predialysis patients (29.5 +/- 9.5 mm Hg). The parathyroid hormone level, cardiac output values and CRF duration were found to be increased in patients with elevated systolic PAP (p < 0.05). AVF flow and AVF duration were positively correlated with systolic PAP in patients receiving hemodialysis (p < 0.05). There was a negative correlation between systolic PAP and residual urine volume (p < 0.05). AVF compression in hemodialysis patients decreased systolic PAP from 36.8 +/- 10.7 to 32.8 +/- 10.5 mm Hg. Systolic PAP values were increased at the end of the study in the predialysis group, whereas they were decreased at the end of the follow-up in the hemodialysis group (36.9 +/- 10.5 and 32.04 +/- 10.5 mm Hg, respectively). CONCLUSIONS: This study demonstrates a high incidence of PH among patients with CRF. CRF duration, AVF flow, parathyroid hormone level and cardiac output may be involved in the pathogenesis of PH. The effective hemodialysis and dry weight reduction decreased systolic PAP values.     

瑞舒伐他汀对慢性心力衰竭合并肾功能不全患者的疗效观察

目的 观察瑞舒伐他汀治疗慢性心力衰竭合并肾功能不全的临床疗效.方法 回顾性分析2010年2月至2013年2月我院住院治疗的72例慢性心力衰竭合并肾功能不全患者的临床记录资料,所有患者均给予心力衰竭基础治疗,给予瑞舒伐他汀的患者作为治疗组,未给予的患者作为对照组.比较治疗6月后两组患者心功能和肾功能的变化.结果 治疗6个月后,治疗组心功能改善的总有效率显著高于对照组（P＜0.05）;左室射血分数较治疗前明显增高（P＜0.05）,左室舒张末期内径、左室收缩末期内径较治疗前缩小（P＜0.05）,且均优于对照组（P＜0.05）;血尿素氮、肌酐、β2-微球蛋白较对照组明显降低（P＜0.05）.结论 在常规抗心衰治疗的基础上联合使用瑞舒伐他汀,可以改善慢性心力衰竭患者的心功能及肾功能.     

Severe metabolic acidosis and renal failure in an HIV-1 patient receiving tenofovir

A 55-y-old male developed severe metabolic acidosis and renal failure during tenofovir therapy. Increased tenofovir exposure due to low body weight and chronic stable renal insufficiency could have enhanced the risk of nephrotoxicity, and creatinine clearance should be estimated before initiation of tenofovir.     

老年慢性心衰患者运动康复的效果

目的：探讨老年慢性心衰患者实施运动康复的安全性及效果。方法：83例老年慢性心衰患者被随机分为常规护理组（41例,常规护理）和运动康复组（42例,在常规护理基础上接受运动训练）。疗程均为8周,随访12个月。患者心功能以纽约心脏病协会（NYHA）分级表示,以超声心动图测定左室射血分数（LVEF）和左室舒张末期内径（LVEDd）,同时测定6min步行距离（6MWD）,血浆脑钠肽（BNP）水平,代谢当量（METs）,明尼苏达心力衰竭生活质量量表（MLHFQ）评分表示健康相关生活质量,记录12个月内的再入院率和死亡率。结果：两组治疗8周时LVEF、LVEDd、NYHA分级均显著改善（P均〈0．05）,且与常规护理组相比,运动康复组LVEF[（54．7±6．2）％比（65．4±8．7）％]、LVEDd[（49．6±8．3）mm比（40．2±9．3）mm]、NYHA分级[（2．7±0．8）级比（1．9±0．9）级]改善更显著（P〈0．05）;6MWD[（122．7±9．2）m比（175．6±8．7）m]和METs[（5．8±1．8）比（8．4±2．4）]也明显增加（P〈0．01）,血浆BNP水平[（43．4±9．8）pg／ml比（31．7±8．9）pg／ml]明显降低（P〈0．05）;运动康复组康复训练中未发生严重不良事件。12个月时,运动康复组MLH-FQ评分明显高于常规护理组[（68．9±7．9）分比（45．65=8．2）分,P〈0．053,因心衰再入院率明显低于常规护理组（9．5％比24．4％,P〈0．05）。结论：对老年慢性心衰患者实施运动康复安全有效,可明显改善心功能,增强运动耐力,提高生活质量。     

心脉隆注射液治疗老年慢性心力衰竭的临床观察

目的：观察心脉隆注射液治疗慢性心力衰竭（CHF）的效果。方法：46例CHF患者被随机分为常规治疗组（21例,常规抗心力衰竭治疗）和心脉隆治疗组（25例,在常规抗心衰治疗基础上加用心脉隆注射液）。疗程2周,在用药前、用药后1～2周进行6min步行试验并进行超声心动图检查。结果：治疗2周后,心脉隆组总有效率明显高于常规治疗组（92.0%比61.9%）;两组患者6min步行距离及LVEF均有明显改善（P〈0.05或〈0.01）,且与常规治疗组比较,心脉隆组6min步行距离[（416.00±39.25）m比（475.00±42.11）m]明显增加,LVEF[（41.23±6.75）%比（48.35±7.5）%]明显提高,P均〈0.05。结论：心脉隆注射液是治疗老年慢性心力衰竭有效的辅助用药。