Lipoprotein (a) in Chronic Renal Failure: Effect of Maintenance Hemodialysis

Background:  Coronary artery disease accounts for significant morbidity and mortality in patients with chronic kidney disease (CKD). Besides the higher prevalence of traditional risk factors, several uremia-related factors may play a role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a) (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well understood. The present work was carried out to study the Lp(a) levels in Stage 4 and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients with Stage 5 CKD.
Methods:  The study subjects included 15 patients with Stage 4 CKD, 15 patients with Stage 5 CKD, and 15 age- and sex-matched healthy controls. Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD were dialyzed two to three times weekly for 4 hr during each session.
Results:  Mean Lp(a) levels were significantly higher in patients with CKD than in control patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 ± 19.5 mg/dL, whereas in Stage 5 CKD the level was 49.0 ± 30.9 and in healthy controls it was 22.2 ± 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant fall in Lp(a) levels by 23.6% (P < 0.001).
Conclusions:  The results of this study show that increases in Lp(a) levels start early during the course of CKD and become more pronounced with increased severity of disease. Initiation of MHD lowers Lp(a) levels and may have a long-term beneficial effect on cardiovascular morbidity and mortality.     

Shock wave effects in biomechanics

Focused shock waves convey energy from a source and deposit it in a localized region remote from the source. This mechanism is used to deliver crushing impulses to kidney stones in patients, but it may also be an undesirable source of tissue injury. Tissue injury occurs in extracorporeal shock wave lithotripsy (ESWL), a popular procedure used around the world to treat kidney stone disease. Shock waves can also be responsible for unexpected symptoms appearing remote from the site of blunt impact trauma. This paper describes two examples of the effects of focused shock waves on tissue. A victim of gunshot wound suffered specific neurological symptoms indicating highly localized injury to the spinal cord remote from the impact point and penetration of the missile. We suggest that wave focusing by thoracic vertebrae can concentrate energy into the spinal canal, with consequent injury to the spinal cord. Impulsive stress in repeated shock waves of order 20 MPa strength administered in ESWL is the mechanical stimulus of injury to the kidney. Research to increase the understanding of the causal relationship between the shock-induced mechanical stimulus and the consequent biomedical symptoms in the shock-wave treatment of kidney stone disease is described. The interaction of focusing shock waves with simple, planar polymeric membranes immersed in tissue-mimicking fluids has been studied. We have explored the nature of membrane failure in both cavitating and non-cavitating fluids. In water, thin nitrocellulose membranes are easily damaged during the passage of a lithotriptor shock wave by the collapse of proximal bubbles generated by cavitation. In uniform non-cavitating liquids, focusing shock waves do not by themselves cause damage, but after passing through tissue or simulated tissue, they do. Shocks with large amplitude and short-rise time (for example, in uniform media) cause no damage in non-cavitating fluids, while long-rise time, dispersed shock waves, though only moderately attenuated, do. A simple model of shearing at small scale provides a framework for accounting for the properties of the scattering medium and the membrane material in dynamic fatigue. The fact that the membranes exhibit fatigue-like behaviour suggests that a definition of dose can be formulated based on Miner’s Law. This definition gives the dose at failure in terms of the stress applied to the membrane by each shock wave and the failure stress. This analysis suggests that ESWL shock waves induce strain rates in tissue of order 10000 s⁻¹ and that behind a tissue, phantom membranes fail after a dose of about 1400 effective shock waves, of the same order as the number of shock waves typically used in lithotripsy therapy and research. Above strain rates of about 40000 s⁻¹, ESWL shocks cause virtually no damage. The author recognizes his colleagues whose work this paper reports, B Carriére, J S Kung, S Wolf, J Cates, A Evan, P Blomgren and D Howard.     

Effects of heavy metal pollution on pigmented macrophages in kidney of Vardar chub (Squalius vardarensis Karaman)

Pollution with heavy metals may influence the immune system of fish, leading to impairment of their health or even increase their mortality. The fish kidney is one of the first fish organs to be affected by water contamination. Amounts of kidney macrophages (MACs), which are involved in fish immune response, as well as the qualitative and quantitative changes in the pigmented MACs in fish kidney, are used as biomarkers of pollution. Therefore, in this study, we have evaluated relative and total volumes of trunk kidney pigmented MACs, and analyzed the pigments accumulated within them. Fish were sampled from two mining impacted rivers, Kriva and Zletovska, highly contaminated with heavy metals, and from one reference river, Bregalnica, in spring and autumn of 2012. We have observed that main pigments found in kidney MACs of Vardar chub were melanin and lipofuscin/ceroid, as well as that relative volumes of MACs ranged from 0.56 to 1.68%. Moreover, the results showed that relative volumes of pigmented MACs were higher in metal contaminated rivers, especially in autumn season in the Zletovska River, concurrently with extremely high metal exposure. In addition, condition factors and kidney somatic indices were found significantly lower in the Zletovska River in both seasons, autumn and spring, possibly also as a consequence of high water pollution. Our data confirm that increase in relative volumes of pigmented MACs may serve as warning sign of potential heavy metal pollution in aquatic environment.     

Humidity‐Tolerant Single‐Stranded DNA‐Functionalized Graphene Probe for Medical Applications of Exhaled Breath Analysis

Highly sensitive and selective chemiresistive sensors based on graphene functionalized by metals and metal oxides have attracted considerable attention in the fields of environmental monitoring and medical assessment because of their ultrasensitive gas detecting performance and cost‐effective fabrication. However, their operation, in terms of detection limit and reliability, is limited in traditional applications because of ambient humidity. Here, the enhanced sensitivity and selectivity of single‐stranded DNA‐functionalized graphene (ssDNA‐FG) sensors to NH₃ and H₂S vapors at high humidity are demonstrated and their sensing mechanism is suggested. It is found that depositing a layer of ssDNA molecules leads to effective modulation of carrier density in graphene, as a negative‐potential gating agent and the formation of an additional ion conduction path for proton hopping in the layer of hydronium ions (H₃O⁺) at high humidity (>80%). Considering that selectively responsive chemical vapors are biomarkers associated with human diseases, the obtained results strongly suggest that ssDNA‐FG sensors can be the key to developing a high‐performance exhaled breath analyzer for diagnosing halitosis and kidney disorder.     

Dietary Conjugated Linoleic Acid Renal Benefits and Possible Toxicity vary with Isomer,Dose and Gender in Rat Polycystic Kidney Disease

Conjugated linoleic acid (CLA) is anti-proliferative and anti-inflammatory in the Han:SPRD-cy rat model of kidney disease. We used different doses of CLA and examined effects on renal histological benefit, the renal PPARgamma system and hepatic and renal levels of CLA isomers. Male and female offspring of Han:SPRD-cy heterozygotes were fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks before dual-energy X-ray absorptiometry, harvest of renal and hepatic tissue for histologic and lipid analysis. Both CLA diets reduced body fat content in both genders but did not change lean body mass. CLA produced a dose dependent reduction in female renal cystic change. CLA reduced fibrosis, but this reduction was significantly less with higher dose in males. CLA reduced macrophage infiltration, tissue oxidized LDL content and proliferation of epithelial cells. Serum creatinine rose significantly in female animals fed CLA diets. CLA treatment did not change PPARgamma activation. A significant negative correlation with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects was identified. CLA reduces histologic renal injury in the Han:SPRD-cy rat model probably inversely proportionate to c9,t11 renal content. Possible functional CLA toxicity at high dose in female animals warrants further exploration.     

Factors affecting anemia management in hemodialysis patients: a single-center experience

The difficulty maintaining hemoglobin (Hgb) within the targets recommended by KDOQI is widely recognized. While factors responsible for erythropoietin resistance have been widely studied, factors responsible for the marked fluctuations and the inability to maintain Hgb within the target range have only begun to be investigated. This study was a cross-sectional review of anemia management in hemodialysis patients. The purpose was to evaluate factors responsible for Hgb decreases of 0.5 or 1.0 g/dL and to determine the primary factors responsible for Hgb decreases below 11 g/dL. Hgb values and clinical events were extracted from patient management databases between January 1, 2005 and November 30, 2006. Isolated events were defined as events that occurred at least 30 days after any previous event and had Hgb measurements within 2 weeks before and after the event. Increasing hospital length of stay and surgical access intervention were the most common events that resulted in a decrease in Hgb. The most common factor present in patients with Hgb decreases below 11 g/dL was the withholding of recombinant human erythropoietin (rHuEPO) within the preceding 2 months. This was the only explanation for the decrease in Hgb to <11 g/dL in 38.5% of such events. The ability to maintain dialysis patients' Hgb in the target range is complicated by intervening acute events that require hospitalization or surgical access interventions. The withholding of rHuEPO appears to be a major factor in Hgb decreases below 11 g/dL.     

Protecting the endothelium: a new focus for management of chronic kidney disease

It is being increasingly recognized that cardiovascular disease (CVD) and its complications are the most important cause of morbidity and mortality in patients with chronic kidney disease (CKD) and dialysis patients. If outcomes for these patients are to be improved, therapeutic strategies at all stages of CKD will have to target the etiologies and mechanisms that lead to CVD. In this review, we focus on the central role of endothelial dysfunction as the critical precursor of CVD. We argue that a better understanding of endothelial dysfunction by nephrologists and dialysis physicians is necessary if there is to be success in limiting the CVD epidemic that kills and maims our patients. The extensive studies to explain the high prevalence of vascular disease in patients with CKD have shown the close relationship among endothelial dysfunction, inflammation, and atherosclerosis. The pathogenesis starts with endothelial cell injury from any of many possible causes, and strategies to reduce the burden of CVD in uremic and dialysis patients must be directed at restoring normal endothelial function or, at the least, preventing aggravation of endothelial damage. At the center of the exploration of endothelial dysfunction and atherosclerosis are oxidative stress and inflammation. Of these, which is the chicken and which is the egg is unknown, but in the setting of uremia, endothelial injury because of free radical, oxidative stress is likely to precede inflammation. The issues raised here are highly complex and most renal practitioners may not have been adequately exposed to the background research underlying current thinking of the pathogenesis of vascular disease. Clearly, progress in management of CVD in patients with CKD will require collaboration with experts in the research and treatment of vascular disease. Nephrologists seeking optimum outcomes for patients with CKD will need to become "endotheliologists" or, at the least, subscribe to a mission "to protect the endothelium."     

High-Density Lipoproteins in Kidney Disease

Decades of epidemiological studies have established the strong inverse relationship between high-density lipoprotein (HDL)-cholesterol concentration and cardiovascular disease. Recent evidence suggests that HDL particle functions, including anti-inflammatory and antioxidant functions, and cholesterol efflux capacity may be more strongly associated with cardiovascular disease protection than HDL cholesterol concentration. These HDL functions are also relevant in non-cardiovascular diseases, including acute and chronic kidney disease. This review examines our current understanding of the kidneys’ role in HDL metabolism and homeostasis, and the effect of kidney disease on HDL composition and functionality. Additionally, the roles of HDL particles, proteins, and small RNA cargo on kidney cell function and on the development and progression of both acute and chronic kidney disease are examined. The effect of HDL protein modification by reactive dicarbonyls, including malondialdehyde and isolevuglandin, which form adducts with apolipoprotein A-I and impair proper HDL function in kidney disease, is also explored. Finally, the potential to develop targeted therapies that increase HDL concentration or functionality to improve acute or chronic kidney disease outcomes is discussed.     

Heme Burden and Ensuing Mechanisms That Protect the Kidney: Insights from Bench and Bedside

With iron at its core, the tetrapyrrole heme ring is a cardinal prosthetic group made up of many proteins that participate in a wide array of cellular functions and metabolism. Once released, due to its pro-oxidant properties, free heme in sufficient amounts can result in injurious effects to the kidney and other organs. Heme oxygenase-1 (HO-1) has evolved to promptly attend to such injurious potential by facilitating degradation of heme into equimolar amounts of carbon monoxide, iron, and biliverdin. HO-1 induction is a beneficial response to tissue injury in diverse animal models of diseases, including those that affect the kidney. These protective attributes are mainly due to: (i) prompt degradation of heme leading to restraining potential hazardous effects of free heme, and (ii) generation of byproducts that along with induction of ferritin have proven beneficial in a number of pathological conditions. This review will focus on describing clinical aspects of some of the conditions with the unifying end-result of increased heme burden and will discuss the molecular mechanisms that ensue to protect the kidneys.     

液相色谱—串联质谱法测定猪可食用组织中氨茶碱残留

目的:研究猪可食用组织中氨茶碱药物残留的定性定量测定方法。方法:建立固相萃取净化结合高效液相色谱—串联质谱法,试样中的氨茶碱药物残留被甲醇溶液提取后,经PRiME HLB固相萃取柱一步净化,随后用C₁₈色谱柱分离,以0.1%甲酸水溶液和乙腈分别作为水相和有机相对氨茶碱进行色谱柱梯度洗脱,利用电喷雾正电压离子化并采用多反应监测模式进行化合物检测,空白基质匹配标准曲线外标法定量。结果:氨茶碱药物在3.5 min内完成仪器分析,不同基质的匹配曲线在0.005～0.1μg/mL质量浓度范围内呈良好的线性关系(R>0.998 0),猪肉、猪肝、猪肾的方法加标平均回收率为87.2%～101.3%,相对标准偏差为0.7%～6.2%(n=6),方法检出限为2μg/kg,定量限为5μg/kg。结论:该方法简便高效、重复性好、灵敏度高,适用于猪的可食用组织中氨茶碱药物残留的定性定量分析。