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.

Relationship between nonalcoholic fatty liver disease and chronic kidney disease could start in childhood

The relationship between nonalcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD)has gained considerable scientific interest in adults over the past few years.However,this association has recently emerged in children.Several published studies have suggested a role for NAFLD as a risk factor for CKD from the earliest age,with a potential influence of the major NAFLD risk polymorphisms,resulting in an increased risk of both cardiovascular and metabolic diseases.In view of the progressive course and increased cardiometabolic risk closely related to NAFLD and CKD,we focused on the link between these diseases in childhood.

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.

Diabetic kidney disease in pediatric patients: A current review

In the last decades,a significant increase in the incidence of diabetic kidney disease(DKD)was observed concomitant with rising diabetes mellitus(DM)incidence.Kidney disease associated with DM in children and adolescents is represented by persistent albuminuria,arterial hypertension,progressive decline in estimated glomerular filtration rate to end-stage renal disease and increased cardiovascular and all-cause morbidity and mortality of these conditions.In medical practice,the common and still the“gold standard”marker for prediction and detection of diabetic kidney involvement in pediatric diabetes is represented by microalbuminuria screening even if it has low specificity to detect early stages of DKD.There are some known limitations in albuminuria value as a predictor biomarker for DKD,as not all diabetic children with microalbuminuria or macroalbuminuria will develop end-stage renal disease.As tubular damage occurs before the glomerular injury,tubular biomarkers are superior to the glomerular ones.Therefore,they may serve for early detection of DKD in both type 1 DM and type 2 DM.Conventional and new biomarkers to identify diabetic children and adolescents at risk of renal complications at an early stage as well as renoprotective strategies are necessary to delay the progression of kidney disease to end-stage kidney disease.New biomarkers and therapeutic strategies are discussed as timely diagnosis and therapy are critical in the pediatric diabetic population.

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.

Demographic Characteristics of Patients and Causes Leading to Chronic Renal Failure in Children Admitted to Mashhad Children Hospital

Background: An irreversible renal function impairment is called chronic renal failure (CRF) which finally leads to the “end-stage renal disease” (ESRD) and requires renal replacement therapies. The aim of this study is to evaluate the incidence, prevalence of epidemiological indicators (age, sex), and causes of chronic renal failure in children in Mashhad (one of the big cities of Iran). Methods: This is a cross-sectional study that was conducted on patients’ records over a seven-year period (2008-2014) in Doctor Sheikh Children’s Hospital of Mashhad. The inclusion criteria were all children under 20 years old diagnosed with ESRD, with a GFR less than 15 ml/min/1.73 m2 who were referred to the hospital during the study period. Patients’ information, such as age, gender, onset of dialysis, causes of constructing renal failure, and positive or negative antigen of hepatitis B was extracted from their records. Data were analyzed using SPSS 16 software. Results: A total of 326 patients were studied, of which, 56.4% were male. 45.1% were from 7 to 18 years. 56.4% of patients were on hemodialysis and others were on peritoneal dialysis. The most common cause of chronic renal failure in the study was respectively reflux nephropathy (32.9%), nephrotic syndrome (8.9%), neurogenic bladder (5.5%), stones (2.5%), glomerulopathy (2.1%) and cystinosis (1.5%) and (20.9%) had unknown cause. During the 7-year period of study considering the treatment outcomes, 69.3% of patients needed to continue the dialysis;10.4% underwent transplantation;10.4% unfortunately died despite of treatment and 1.5% were cured. Conclusions: It is hoped that considering the clinical symptoms of children with chronic renal failure and the diagnosis of the cause, we can reduce complications of the disease with a quick diagnosis and treatment, as well as appropriate follow-up.

激素序贯疗法联合免疫球蛋白治疗儿童川崎病的效果

目的观察激素序贯疗法联合免疫球蛋白治疗儿童川崎病的效果。方法前瞻性选择2022年1—12月医院收治的100例经免疫球蛋白治疗无应答的川崎病患儿,按照随机数字表法分为对照组与观察组,各50例。对照组接受免疫球蛋白冲击治疗,观察组在对照组基础上接受激素序贯疗法。观察患儿症状消退时间。比较两组治疗前、治疗2周后炎症指标[C反应蛋白(CRP)、红细胞沉降率(ESR)、白细胞计数(WBC)]、细胞因子[基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)]水平,统计治疗期间不良反应发生情况。随访12周,记录心血管损害情况。结果观察组各主要症状消退时间短于对照组(P<0.05)。治疗后,两组CRP、ESR、WBC、MMP-9、VEGF低于治疗前,且观察组低于对照组(P<0.05)。两组治疗期间不良反应发生率差异无统计学意义(P>0.05)。随访12周,观察组心血管损害总发生率低于对照组(P<0.05)。结论激素序贯疗法联合免疫球蛋白治疗川崎病免疫球蛋白无应答的患儿,可促进症状改善,减轻炎症反应,降低MMP-9、VEGF表达,降低心血管损害风险,安全性可。

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.

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.

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.

嗜酸性粒细胞高低对慢性阻塞性肺疾病急性加重期是否应用激素的指导价值

目的探讨外周血嗜酸性粒细胞高低对慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)是否应用激素的指导价值。方法收集2016-01至2017-10在医院呼吸科住院的慢性阻塞性肺疾病急性加重患者224例,根据外周血嗜酸性粒细胞是否升高及是否采用激素治疗。分成4组:血EOS增高激素治疗组(1组),血EOS正常激素治疗组(2组),血EOS增高非激素治疗组(3组),血EOS正常非激素治疗组(4组)。收集患者性别、年龄、合并症、CAT评分、血气分析、肺功能及一氧化氮呼气试验。4组均给予吸氧,抗炎,平喘及化痰等一般治疗外,1组及2组加用激素治疗,治疗1周后复查,对4组的FENO、评估CAT评分;计算住院时间及出院3个月后再住院率。结果4组年龄、性别、血气分析,血红蛋白等方面差异无统计学意义,4组治疗前后FENO及血EOS存在统计学差异(P<0.05)。平均住院时间及3个月再住院率方面,1组患者平均住院时间最短,且3个月再住院率均低于其他3组,差异具有统计学意义(P<0.05)。结论外周血嗜酸性粒细胞增高的慢性阻塞性肺疾病急性加重期患者宜应用激素治疗。

慢性肾脏病患儿小剂量甲状腺素治疗的作用及甲状腺激素水平变化的意义

目的:探讨慢性肾脏病小剂量甲状腺素治疗的作用和甲状腺激素水平变化的意义。方法:患儿92例慢性肾脏病患儿随机分为甲状腺素治疗组和对照组,各46例,均予常规治疗。治疗组加服左旋甲状腺素组25～50μg/d。随访至少1月,比较2组的临床疗效,放射免疫分析法检测甲状腺素的水平。结果:治疗后1、2、4周,两组尿蛋白、尿潜血定性、Hb值及白蛋白水平无明显变化。但2组SCr与BUN在治疗后1周即均下降,并持续至第4周(P<0.05),而治疗组下降更为明显(P<0.05)。甲状腺功能检测显示治疗组1周后FT3、FT4上升,TSH下降,并持续至第4周(P<0.05),与对照组比水平也均有改善(P<0.05)。所有患者FT3与SCr浓度之间呈负相关,r值为-0.71(t=6.147,P=0.012)。结论:小剂量甲状腺素对小儿慢性肾脏病有治疗作用,其甲状腺素水平可以作为疗效检测和预后评价的一种指标。

慢性肾脏病合并甲状腺功能减退患者应用左甲状腺激素替代治疗的临床意义

目的:研究在适当的左甲状腺激素替代治疗后,能否逆转或延缓慢性肾脏病进展。方法:根据eGFR将CKD分为CKD2期组、CKD3期组、CKD4期组。分别比较治疗前后的患者TSH、FT3、FT4、eGFR的变化。再将每组患者根据甲状腺功能分为:a、b两个亚组进行比较。结果:①CKD4期组患者年龄明显大于其余两组;CKD4期组患者TSH明显高于其余两组,FT3、FT4明显低于其他两组。CKD2期组治疗后,eGFR改善不显著;CKD3及CKD4期组治疗后,eGFR显著改善。②分为a、b亚组进行分析。将CKD2a、CKD2b、CKD3a、CKD3b、CKD4a、CKD4b:其中CKD2b、CKD4b组患者治疗后,eGFR改善不显著;CKD2a、CKD3a、CKD3b、CKD4a组患者治疗后,eGFR均显著改善。无论CKD2期、CKD3期及CKD4期组患者,存在明显甲状腺功能减退的患者比亚临床甲状腺功能减退的患者eGFR改善更明显。结论:①CKD合并甲状腺功能减退的患者,经左甲状腺激素替代治疗两个月后,甲状腺功能均显著改善;②CKD3期组和CKD4期组患者经左甲状腺激素替代治疗后,eGFR改善较治疗前均有显著差异;③三组患者治疗前后eGFR的变化(即ΔeGFR),其中CKD3期组患者最为显著;④经左甲状腺激素替代治疗两个月后,临床甲状腺功能减退亚组较亚临床甲状腺功能减退亚组的甲状腺功能及eGFR改善更为显著。

中药灌肠对慢性肾脏疾病患者血清甲状旁腺素的清除作用

目的观察中药灌肠对慢性肾脏疾病(CKD)患者血清甲状旁腺素(PTH)的清除作用。方法将88例CKD患者随机分为2组,对照组45例予常规治疗,治疗组43例在对照组治疗基础上予中药灌肠治疗,2组均治疗12周。比较2组中医证候疗效,观察2组治疗前后血清肌酐(Cr)、尿素氮(BUN)及PTH变化。结果 2组中医证候总有效率比较差异有统计学意义(P<0.05),治疗组中医证候疗效优于对照组。治疗组治疗后Cr、BUN及PTH均较本组治疗前、对照组治疗后降低(P<0.05)。结论中药灌肠可有效改善CKD患者肾功能,降低Cr、BUN等小分子尿毒症毒素的浓度,更可以降低血清PTH浓度,可有效配合血液透析滤过等肾脏替代治疗。

慢性阻塞性肺疾病大鼠支气管肺组织EGR-1、PDGF-BB的表达及普米克令舒干预的影响

目的:探讨早期生长反应因子-1(EGR-1)、血小板源性生长因子-BB(PDGF-BB)在慢性阻塞性肺疾病(COPD)发病机制中的作用,并评价普米克令舒在COPD治疗中的效果。方法:用烟熏加气管内灌注内毒素的方法复制COPD大鼠模型,造模完成后给予雾化吸入普米克令舒两周,观察1周、2周、4周组,普米克干预组及各对照组大鼠的支气管肺组织病理变化,进行免疫组织化学染色和定量图像分析,以检测EGR-1、PDGF-BB蛋白质表达水平。结果:1各时间点模型组大鼠均有不同程度的COPD的病理改变,各对照组病理结构基本正常。普米克干预组与干预对照组相比病理表现无明显改善。2各时间点模型组大鼠肺间质结缔组织、支气管壁及小血管壁内可见棕黄色颗粒状或细丝状的EGR-1、PDGF-BB蛋白阳性染色。模型1周、2周、4周组大鼠的支气管肺组织中EGR-1、PDGF-BB的积分光密度(IOD)值与各对照组相比均有显著性差异。模型1周、2周、4周组大鼠的EGR-1、PDGF-BB的IOD值也有显著性差异。3雾化吸入普米克令舒后EGR-1、PDGF-BB表达与对照组相比均有明显下降。4EGR-1和PDGF-BB表达呈正相关。结论:1EGR-1、PDGF-BB可能参与COPD气道炎症进展。2EGR-1与PDGF-BB的表达水平呈正相关,二者的诱导表达机制尚需进一步研究。3COPD激素吸入两周可以降低EGR-1、PDGF-BB的表达水平,但并未引起明显病理改变。