Complexity and Management of Chronic Kidney Disease

Chronic Kidney Disease (CKD) is ongoing damage of the kidneys, which affects their ability to filter the blood the way they should. Worldwide CKD is considered as the 16th leading cause of death and affects 8% - 16% of the population. CKD often goes unnoticed and is revealed as an incidental finding. Healthcare providers diagnose the condition as CKD based on persistent abnormal kidney function tests revealing kidney damage markers > 3 months, urine albumin creatinine ratio (UACR) > or equal to 30 mg/g per 24 hours, and GFR < 60 mL/min/1.73m2. In this article, we have discussed chronic kidney disease in terms of kidney physiology, chronic kidney disease pathophysiology, etiology, diagnosis, signs and symptoms, and management.

Oral alkali therapy and the management of metabolic acidosis of chronic kidney disease:A narrative literature review

Chronic metabolic acidosis is a common complication seen in advanced chronic kidney disease(CKD). There is currently no consensus on its management in the Republic of Ireland. Recent trials have suggested that appropriate active management of metabolic acidosis through oral alkali therapy and modified diet can have a deterring impact on CKD progression. The potential benefits of treatment include preservation of bone health and improvement in muscle function; however,present data is limited. This review highlights the current evidence,available primarily from randomised control trials(RCTs) over the last decade,in managing the metabolic acidosis of CKD and outlines ongoing RCTs that are promising. An economic perspective is also briefly discussed to support decision-making.

Anti-hepatitis C virus therapy in chronic kidney disease patients improves long-term renal and patient survivals

BACKGROUND Hepatitis C virus (HCV) infection is a documented risk factor for chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). However, to date there are no reports on the long-term hard endpoints (ESRD and death) of anti-HCV therapy [interferon-based therapy (IBT) or new direct-acting antivirals] in CKD patients. Direct-acting antivirals are not available in Taiwan’s singlepayer national health insurance database currently released for research. Therefore, we hypothesized that a retrospective analysis of the long-term outcomes of IBT in CKD patients will serve as a proxy for direct-acting antivirals to increase our understanding of progression to ESRD following HCV infection. AIM To evaluate the long-term outcomes (ESRD and death) of anti-HCV therapy, especially IBT, in HCV-infected patients with stage 1-5 CKD. METHODS We analyzed 93894 Taiwan Residents adults diagnosed with CKD and without HBV infection. Of these, 4.9% were infected with HCV. Of the 4582 HCV-infected CKD patients, 482 (10.5%) received IBT (treated cohort). They were matched 1:4 with 1928 untreated HCV-infected CKD patients (untreated cohort) by propensity scores and year, which further matched 1:2 by propensity scores with 3856 CKD patients without HCV infection (uninfected cohort). All participants were followed until the occurrence of ESRD, death, or the end of 2012. The association between HCV infection, IBT use, and risks of ESRD and death was analyzed using competing risk analysis. RESULTS Taking the uninfected cohort as a reference, the adjusted hazard ratios for ESRD, after adjusting for competing mortality, were 0.34 (0.14-0.84, P = 0.019) and 1.28 (1.03-1.60, P = 0.029) in the treated and untreated cohorts, respectively. The treated cohort had a 29%(0.54-0.92, P = 0.011) decrease in mortality compared to the untreated cohort, in which the mortality was 31%(1.18-1.45, P < 0.001) higher than in the uninfected cohort. The reduced risks of ESRD (0.14, 0.03–0.58, P = 0.007) and death (0.57, 0.41-0.79, P = 0.001) were greatest in HCV-infected CKD patients who received at least 4 mo of IBT, which accounted for 74% of the treated cohort.CONCLUSION Adequate anti-HCV therapy in CKD patients improves long-term renal and patient survival.

Sleep disorders and chronic kidney disease

Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease(CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.

Chronic kidney disease prediction is an inexact science: The concept of “progressors” and “nonprogressors”

In 2002,the National Kidney Foundation Kidney Disease Outcomes Quality Initiative(NKF KDOQI)instituted new guidelines that established a novel chronic kidney disease(CKD)staging paradigm.This set of guidelines,since updated,is now very widely accepted around the world.Nevertheless,the authoritative United States Preventative Task Force had in August 2012acknowledged that we know surprisingly little about whether screening adults with no signs or symptoms of CKD improve health outcomes and that we deserve better information on CKD.More recently,the American Society of Nephrology and the American College of Physicians,two very well respected United States professional physician organizations were strongly at odds coming out with exactly opposite recommendations regarding the need or otherwise for"CKD screening"among the asymptomatic population.In this review,we revisit the various angles and perspectives of these conflicting arguments,raise unanswered questionsregarding the validity and veracity of the NKF KDOQI CKD staging model,and raise even more questions about the soundness of its evidence-base.We show clinical evidence,from a Mayo Clinic Health System Renal Unit in Northwestern Wisconsin,United States,of the pitfalls of the current CKD staging model,show the inexactitude and unpredictable vagaries of current CKD prediction models and call for a more cautious and guarded application of CKD staging paradigms in clinical practice.The impacts of acute kidney injury on CKD initiation and CKD propagation and progression,the effects of such phenomenon as the syndrome of late onset renal failure from angiotensin blockade and the syndrome of rapid onset end stage renal disease on CKD initiation,CKD propagation and CKD progression to end stage renal disease all demand further study and analysis.Yet more research on CKD staging,CKD prognostication and CKD predictions are warranted.Finally and most importantly,cognizant of the very serious limitations and drawbacks of the NKF K/DOQI CKD staging model,the need to individualize CKD care,both in terms of patient care and prognostication,cannot be overemphasized.

Reno protective role of amlodipine in patients with hypertensive chronic kidney disease

Chronic kidney disease(CKD)and hypertension(HTN)are closely associated with an overlapping and intermingled cause and effect relationship.Decline in renal functions are usually associated with a rise in blood pressure(BP),and prolonged elevations in BP hasten the progression of kidney function decline.Regulation of HTN by normalizing the BP in an individual,thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease,can be effectively achieved by the anti-hypertensive use of calcium channel blockers(CCBs).Use of dihydropyridine CCBs such as amlodipine(ALM)in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes.Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects.In comparison to other counterparts,ALM displays robust reduction in risk of cardiovascular endpoints,particularly stroke,and in patients with renal impairment.ALM with its longer half-life displays effective BP control over 24-h,thereby reducing the progression of endstage-renal disease.In conclusion,compared to other classes of CCBs,ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.

Kidney disease in non-kidney solid organ transplantation

Kidney disease after non-kidney solid organ transplantation(NKSOT)is a common post-transplant complication associated with deleterious outcomes.Kidney disease,both acute kidney injury and chronic kidney disease(CKD)alike,emanates from multifactorial,summative pre-,peri-and post-transplant events.Several factors leading to kidney disease are shared amongst solid organ transplantation in addition to distinct mechanisms unique to individual transplant types.The aim of this review is to summarize the current literature describing kidney disease in NKSOT.We conducted a narrative review of pertinent studies on the subject,limiting our search to full text studies in the English language.Kidney disease after NKSOT is prevalent,particularly in intestinal and lung transplantation.Management strategies in the peri-operative and post-transplant periods including proteinuria management,calcineurin-inhibitor minimization/sparing approaches,and nephrology referral can counteract CKD progression and/or aid in subsequent kidney after solid organ transplantation.Kidney disease after NKSOT is an important consideration in organ allocation practices,ethics of transplantation.Kidney disease after SOT is an incipient condition demanding further inquiry.While some truths have been revealed about this chronic disease,as we have aimed to describe in this review,continued multidisciplinary efforts are needed more than ever to combat this threat to patient and allograft survival.

Effect of thermal therapy using hot water bottles on brain natriuretic peptide in chronic hemodialysis patients

Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.

Latin American Dialysis and Transplant Registry:Experience and contributions to end-stage renal disease epidemiology

In 2015, 634387 million people(9% of the world's population) resided in Latin America(LA), with half of those populating Brazil and Mexico. The LA Dialysis and Transplant Registry was initiated in 1991, with the aim of collecting data on renal replacement therapy(RRT) from the 20 LA-affiliated countries. Since then, the Registry has revealed a trend of increasing prevalence and incidence of end-stage kidney disease on RRT, which is ongoing and is correlated with gross national income, life expectancy at birth, and percentage of population that is older than 65 years. In addition, the rate of kidney transplantation has increased yearly, with > 70% being performed from deceased donors. According to the numbers reported for 2013, the rates of prevalence, incidence and transplantation were(in patients per million population) 669, 149 and 19.4, respectively. Hemodialysis was the treatment of choice(90%), and 43% of the patients undergoing this treatment was located in Brazil; in contrast, peritoneal dialysis prevailed in Costa Rica, El Salvador and Guatemala. To date, the Registry remains the only source of RRT data available to healthcare authorities in many LA countries. It not only serves to promote knowledge regarding epidemiology of end-stage renal disease and the related RRT but also for training of nephrologists and renal researchers, to improve understanding and clinical application of dialysis and transplantation services. In LA, accessibility to RRT is still limited and it remains necessary to develop effective programs that will reduce risk factors, promote early diagnosis and treatment of chronic kidney disease, and strengthen transplantation programs.

Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） and CCB （i.e.,ACEI/ARB ＋ CCB） with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods：Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials （RCTs） of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease （ESRD）,cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate （GFR）,and adverse events were extracted.Results：Based on seven RCTs with 628 patients,ACEI/ARB ＋ CCB did not show additional benefit for the incidence of ESRD （risk ratio [RR] =0.84;95% confidence interval [CI]：0.52-1.33） and cardiovascular events （RR =0.58;95% CI：0.21-1.63） significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP （weighted mean difference [WMD] =-1.28 mmHg;95% CI：-3.18 to-0.62）,proteinuria （standard mean difference =-0.55;95% CI：-1.41 to-0.30）,GFR （WMD =-0.32 ml/min;95% CI：-1.53 to-0.89）,and occurrence of adverse events （RR =1.05;95% CI：0.72-1.53）.However,ACEI/ARB ＋ CCB showed a greater reduction in systolic BP （WMD =-4.46 mmHg;95% CI：-6.95 to-1.97）,compared with ACEI/ARB monotherapy.Conclusion：ACEI/ARB ＋ CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

Driving role of macrophages in transition from acute kidney injury to chronic kidney disease

Acute kidney injury(AKI),characterized by acute renal dysfunction,is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease(CKD).Regardless of the initial insults,the progression of CKD after AKI involves multiple types of cells,including renal resident cells and immune cells such as macrophages.Recently,the involvements of macrophages in AKI-to-CKD transition have garnered significant attention.Furthermore,substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis.In this review,we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization,and transdifferentiation in the development of AKI-to-CKD transition.In addition,the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.

Dyslipidemia promotes the progression of chronic kidney disease

Dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, and low high-densitylipoprotein （HDL） cholesterinemia, is a key risk factor to atherosclerosis. The detrimental effect of elevated low-density lipoprotein （LDL） cholesterol and/or decreased HDL cholesterol on cardiovascular disease risk had been well established from previous studies.1 Recently, emerging evidences suggest that dyslipidemia may also be an important contributor to morbidity and mortality of chronic kidney disease （CKD）, which has received more and more attention as the prevalence of CKD increases.

Renal Replacement Therapy in Qatar—Past, Present and Future

The economic development of Qatar alongside the resultant lifestyle changes in the last few decades has contributed to increasing rates of obesity, diabetes mellitus and hypertension with consequent increased incidence and prevalence of chronic kidney disease and end-stage-renal-disease (ESRD). This article describes renal replacement therapy (RRT) services in Qatar and their evolution in response to challenges posed by the growth of ESRD with reference to regional and international data. It covers the history of RRT, highlighting significant advances in chronological order, as well as providing an overview of the current status of RRT in the multicultural and socioeconomically diverse society that inhabits Qatar. Finally, it casts a glance into the future, predicting how RRT services will further evolve to address the current limitations.

Diabetic Nephropathy and Management

Chronic kidney disease affects people worldwide. Approximately 1 out of 3 adults with diabetes have kidney disease. Among several etiological factors for CKD, diabetes mellitus (DM) and hypertension are the main factors. These factors not only cause CKD but are also responsible for several complications related to CKD. In this article, we have reviewed Diabetic Nephropathy (DN) in terms of etiology, pathophysiology, diagnosis, management, current guidelines for diabetic nephropathy management, and some of the research study findings. Diabetic nephropathy (DN) is the chief factor for end-stage renal disease (ESRD) development across the globe. The primary cause of DN is Diabetes Mellitus, which is an autoimmune lifestyle disorder having several etiological factors. Checking for urine albuminuria, estimated GFR (eGFR), and blood glucose are unswerving tests for DN diagnosis and subsequent monitoring. Controlling hyperglycemia, blood pressure, and proteinuria are critical in stopping the progression of DKD. Clinical practice and evidence-based medicine demonstrated that early diagnosis followed by treatment can prevent or halt DKD progression.

牛大力祛痰、镇咳和平喘作用的实验研究

【目的】观察牛大力的祛痰、镇咳及平喘作用。【方法】通过小鼠气管酚红法、家鸽纤毛运动实验、小鼠浓氨水引咳法、豚鼠枸橼酸引咳法及豚鼠组胺—乙酰胆碱超声雾化法观察牛大力的祛痰镇咳平喘作用。【结果】牛大力能显著增加小鼠气管酚红排泌量,促进家鸽气管内墨汁运动,减少氨水引发小鼠和枸橼酸引发豚鼠咳嗽反应的次数,延长咳嗽潜伏期,对抗组胺—乙酰胆碱引起的豚鼠支气管哮喘(均P<0.05或P<0.01)。【结论】牛大力具有一定的祛痰、镇咳及平喘作用。

生脉胶囊对压力超负荷慢性心衰大鼠心室重构的影响

【目的】观察生脉胶囊对压力超负荷慢性心力衰竭(CHF)大鼠心室重构的影响。【方法】SD大鼠75只,采用腹主动脉缩窄法复制大鼠慢性心力衰竭模型,设立假手术组、心衰模型组、生脉胶囊组、卡托普利组、生脉胶囊加卡托普利组,分组治疗7周时进行超声心动图检查,以左室舒张末期内径(dLVD)、室间隔舒张末期厚度(dIVST)、舒张末期容积(VED)、射血分数(pEF)、左室短轴缩短率(pFS)为指标,并计算左室质量指数(Im,LV)。【结果】模型组Im,LV、dLVD、dIVST、VED值均高于假手术组(P<0.05或P<0.01),生脉胶囊、卡托普利、生脉胶囊加卡托普利均能使其降低(P<0.05或P<0.01),且作用相同;模型组pEF、pFS均低于假手术组(P<0.01),生脉胶囊、生脉胶囊加卡托普利均能提高pEF值(P<0.01),且生脉胶囊加卡托普利的作用优于卡托普利(P<0.05);生脉胶囊、生脉胶囊加卡托普利均能提高pFS值(P<0.05或P<0.01)。【结论】生脉胶囊可改善慢性心力衰竭大鼠的心脏射血功能和心脏结构,具有抗心室重构的作用。

喘可治注射液对慢性阻塞性肺疾病大鼠肺组织STAT4、STAT6蛋白表达的影响

【目的】探讨喘可治注射液对慢性阻塞性肺疾病(COPD)大鼠肺组织STAT4、STAT6蛋白表达的作用。【方法】采用香烟烟雾吸入加脂多糖气管滴注法复制COPD大鼠模型,随机分为正常组、模型组、卡介菌多糖核酸注射液组、喘可治注射液治疗组(中药高、中、低剂量组,7.5、3.75、1.875 mg·kg-1·d-1腹腔注射给药)。采用Western blot蛋白质印迹法检测大鼠肺组织STAT4、STAT6蛋白表达,观察喘可治注射液对COPD大鼠肺组织STAT4、STAT6蛋白表达的影响。【结果】与正常组比较,COPD大鼠肺组织STAT4蛋白表达亢进(P<0.01),STAT6蛋白表达受抑(P<0.01);喘可治注射液能抑制大鼠STAT4蛋白表达(P<0.01),促进STAT6蛋白表达(P<0.05或P<0.01),作用效果与卡介菌多糖核酸注射液相仿(P>0.05);STAT4、STAT6蛋白表达呈负相关性,且喘可治注射液作用后STAT6蛋白表达量越多,STAT4相应的表达量越少。【结论】喘可治注射液防治COPD的可能作用机制是通过影响STAT4和STAT6蛋白表达,干扰IL-12/STAT4和IL-4/STAT 6信号通路对Th1和Th2细胞基因表达,抑制Th1极化,进而调节Thl/Th2细胞分化失衡,减轻T细胞介导的肺部炎症和病理损害作用。

加味四逆散对心理应激损伤大鼠海马nNOS表达的影响

【目的】观察调肝治法方药——加味四逆散对慢性心理应激损伤大鼠海马神经元神经型一氧化氮合酶(nNOS)表达的影响。【方法】取W istar大鼠24只随机分为3组:正常组(不施加任何刺激)、模型组(给予21 d的随机应激刺激)、加味四逆散组(每次刺激前1 h灌胃中药1次,剂量为3.38 g/只)。正常组及模型组每次灌胃等容积生理盐水。采用免疫组织化学方法检测nNOS表达。【结果】3组大鼠海马的CA3区锥体细胞均有nNOS表达,而模型组表达的强度显著高于正常组,其阳性细胞数及阳性累积分显著性增多(P<0.01);加味四逆散可显著性降低大鼠海马nNOS表达,减少其阳性细胞数及阳性累积分(P<0.01)。【结论】加味四逆散改善慢性心理应激的作用与其能抑制大鼠海马神经元nNOS的高表达,从而避免NO升高损害细胞有关。

益气化痰方对慢性阻塞性肺疾病大鼠肺泡灌洗液中AQP5、TNF-α和MUC5AC的影响

【目的】观察益气化痰方对慢性阻塞性肺疾病(COPD)大鼠肺泡灌洗液(BALF)水通道蛋白5(AQP5)及其上游信号通道调节因子肿瘤坏死因子-α(TNF-α)和下游信号通道调节因子黏蛋白5AC(MUC5AC)的调节作用。【方法】选用SD大鼠,随机分为空白组,模型组,益气化痰方低、中、高剂量组(剂量分别为7.398、36.99、73.98 g·kg-1·g-1)。除空白组外,其他组均采用香烟熏结合脂多糖气管滴入法复制COPD大鼠模型。采用益气化痰中药煎剂治疗COPD大鼠30 d后取材,观察肺组织苏木精—伊红(HE)染色,采用免疫组织化学法观察AQP5、TNF-α、MUC5AC的表达,酶联免疫吸附法(ELISA)测定大鼠肺泡灌洗液(BALF)中AQP5、TNF-α和MUC5AC的含量。【结果】益气化痰汤各剂量组均可改善COPD大鼠的肺组织病理损害,减弱肺组织MUC5AC、TNF-α表达,增强AQP5表达。与空白组比较,模型组肺组织BALF中AQP5浓度显著下降(P<0.01),TNF-α和MUC5AC浓度显著升高(P<0.01)。与模型组比较,益气化痰方低、中、高剂量组肺组织BALF中AQP5浓度显著升高(P<0.01),TNF-α和MUC5AC浓度显著下降(P<0.01)。与低、中剂量组比较,益气化痰汤高剂量组作用显著(P<0.01)。【结论】益气化痰方对COPD的疗效可能与水通道转运密切相关。

肺康颗粒对慢阻肺模型大鼠气道重塑及转化生长因子β_1的影响

【目的】观察肺康颗粒对慢性阻塞性肺疾病(COPD)模型大鼠气道重塑及转化生长因子-β1(TGFβ-1)的影响。【方法】将清洁级SD大鼠40只随机分为正常对照组、COPD模型组,肺康颗粒高、低剂量组(剂量分别为13、3.25g.kg-1.d-1),每组10只。采用熏香烟、气道内多次滴入脂多糖及灌服番泻叶法复制大鼠COPD肺脾两虚型模型。光镜下观察各组大鼠肺组织病理形态学变化并测量肺组织小气道管壁厚度;采用免疫组织化学法并结合图像分析技术测定大鼠肺组织、肺泡巨噬细胞、支气管黏膜上皮TGFβ-1的表达。【结果】与正常对照组比较,模型组大鼠小气道管壁厚度及支气管肺组织TGFβ-1的表达均有显著性升高(P<0.05);肺康颗粒高、低剂量组上述指标均显著低于模型组(P<0.05);但肺康颗粒高、低剂量组间支气管肺组织TGFβ-1表达无显著性差异(P>0.05)。模型组大鼠气道和肺组织出现慢性炎症改变和结构破坏,肺康颗粒高、低剂量组对上述病理变化有明显改善作用。【结论】肺康颗粒治疗COPD的作用与其能在一定程度上改善模型大鼠的气道重塑,降低TGFβ-1的表达有关。