Arterial stiffness,vascular calcification and bone metabolism in chronic kidney disease

Patients with chronic kidney disease (CKD) have an extremely poor cardiovascular outcome. Arterial stiffness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcification in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the definition of “CKD mineral bone disorder” was created recently, underlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We overview a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyrophosphates, matrix Gla protein, osteopontin, fibroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcification and we evaluate their connection to impaired arterial stiffness in the mirror of recent scientific results.     

Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study

AIM: To compare anemia prevalence between matched chronic kidney disease (CKD) patients with and without diabetes mellitus (DM) and to assess factors associated with anemia development. METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate (eGFR). Prevalence of anemia (hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia. RESULTS: The total prevalence of anemia was higher in diabetics (47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3 (53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a (60.4% vs 26.4%, P < 0.001), whereas it was non-significantly higher in Stage 4 (61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM (OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4 (Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron (OR = 0.976, 95%CI: 0.968-0.985 per mg/dL increase) were independently associated with anemia. CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.     

Periodontitis: Tip of the iceberg in chronic kidney disease

The prevalence of chronic kidney disease(CKD)is constantly escalating not only in industrialized countries but throughout the world.It is of major significance because of to its high morbidity and mortality.Strategies to tackle this worldwide health problem include identification of its associated risk factors,comorbidities,and complications as well as proper management to handle all the pertinent issues.Periodontal disease,a treatable infectious state of the dental supporting tissues,is common in CKD patients.Its association with CKD is believed to be in a reciprocal or bidirectional fashion and has been massively studied.This paper,therefore,aims to review the recent evidence pertaining to the association between periodontal disease and a variety of renal illnesses.Most of the current evidence was collected from cross-sectional studies and clinical trials.There is substantial evidence indicating that periodontal disease contributes markedly to the chronic systemic inflammatory burden,leading to cardiovascular and cerebrovascular complications,the principal causes of death among chronic renal disease patients.Furthermore,several studies demonstrated that proper periodontal intervention could help improve systemic inflammation and even nutritional status among CKD patients,resulting in a better quality of life.Suggestions have been made that periodontal disease should be diagnosed early,and managed and controlled to,atleast,eradicate a source of inflammation in this population.Awareness of such an important issue should be increased in the relevant medical personnel.     

A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease

AIM: To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD).METHODS: This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure.RESULTS: Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001).CONCLUSION: This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.     

Nephroprevention in the oldest old with chronic kidney disease:Special considerations

Nephroprevention strategies are crucial for handling chronic kidney disease(CKD) complications, and slowing its progression. However, these preventative measures should be guided by major geriatrics principles in order to help nephrologists to adequately handle the oldest old with CKD. These geriatric concepts consist of taking into account the relevance of choosing an individualized therapy, handling clinical frailty, and keeping a geriatric perspective which means that a good quality of life is sometimes a more important therapeutic objective inoctogenarians than merely prolonging life. Even though nephroprevention strategies for treating the oldest old with CKD are basically similar to those applied to younger patients such as low sodium and protein diet, optimized hemoglobin levels, blood pressure and metabolic control, the treating physician or care provider must at all times be ready to make fundamental adjustments and tweak patient care paradigms and objectives if and when the initial therapeutic options applied have caused unintended clinical consequences and complications. Additionally, the sarcopenia status should also be evaluated and treated in very old CKD patients.     

Cardiovascular co-morbidity in chronic kidney disease: Current knowledge and future research needs

Chronic kidney disease (CKD) is recognised as a health concern globally and leads to high rates of morbidity, mortality and healthcare expenditure. CKD is itself an independent risk factor for unfavorable health outcomes that include cardiovascular disease (CVD). Coronary artery disease is the primary type of CVD in CKD patients and a significant cause of death among renal transplant patients. Traditional and non-traditional risk factors for CVD exist in patients with CKD. Traditional factors include smoking, hypertension, dyslipidemia and diabetes which are highly prevalent in CKD patients. Non-traditional risk factors of CKD are mainly uraemia-specific and increase in prevalence as kidney function declines. Some examples of uraemia-specific risk factors that have been well documented include low levels of haemoglobin, albuminuria, and abnormal bone and mineral metabolism. Therapeutic interventions targeted at more traditional risk factors which contribute to CVD, have not had the desired effect on lowering CVD events and mortality in those suffering with CKD. Future research is warranted to delineate clear evidence to the benefit of modifying non-traditional risk factors.     

Urgent call for reconsideration of chronic kidney disease

Circulating toxins namely: free radicals, cytokines and metabolic products induce glomerular endothelial dysfunction, hemodynamic maladjustment and chronic ischemic state;this leads to tubulointerstitial fibrosis in chronic kidney disease (CKD). Altered vascular homeostasis observed in late stage CKD revealed defective angiogenesis and impaired nitric oxide production explaining therapeutic resistance to vasodilator treatment in late stage CKD. Under current practice, CKD patients are diagnosed and treated at a rather late stage due to the lack of sensitivity of the diagnostic markers available. This suggests the need for an alternative therapeutic strategy implementing the therapeutic approach at an early stage. This view is supported by the normal or mildly impaired vascular homeostasis observed in early stage CKD. Treatment at this early stage can potentially enhance renal perfusion, correct the renal ischemic state and restore renal function. Thus, this alternative therapeutic approach would effectively prevent end-stage renal disease.     

Lipid abnormalities in kidney disease and management strategies

Patients with kidney diseases continue to experience significant cardiovascular disease(CVD) morbidity and mortality. Although there are many important risk factors playing a role in the pathogenesis of CVD in chronic kidney disease(CKD) patients, dyslipidemia(elevated triglycerides, elevated oxidized low-densitylipoprotein and low/dysfunctional low high-density) represents one of the modifiable risk factors. Renal failure patients have unique lipid abnormalities which not only have complex role in pathogenesis of CVD but also cause relative resistance to usual interventions. Most of the randomized trials have been in hemodialysis population and data from CKD non-dialysis, peritoneal dialysis and renal transplant populations is extremely limited. Compared to general population, evidence of mortality benefit of lipid lowering medications in CKD population is scarce. Future research should be directed towards establishing long term benefits and side effects of lipid lowering medications, through randomized trials, in CKD population.     

Stop chronic kidney disease progression: Time is approaching

Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.     

Health literacy in kidney disease: Review of the literature and implications for clinical practice

Health literacy is the capacity of an individual to understand information related to a disease in order to make an informed decision. In patients with kidney diseases, studies have reported increasing impact of limited health literacy on health outcomes. Our paper discusses current literature on health literacy in kidney diseases.     

Measurement of the intestinal permeability in chronic kidney disease

AIM: To evaluate methods measuring the intestinal per-meability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD. METHODS: We reviewed the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and performed a systematic literature search through MEDline and EMBASE. All controlled trials and cohort studies using non-invasive methods to assess intestinal permeability in CKD patients were included. Excluded were: Conference abstracts and studies including patients younger than 18 years or animals. From the included studies we summarized the used methods and their advantages and disadvantages. For the comparison of their results we divided the included studies in two categories based on their included patient population, either assessing the intestinal permeability in mild to moderate CKD patients or in end stage renal disease (ESRD) patients. Results were graphically displayed in two plots, one comparing the intestinal permeability in mild to moderate CKD patients to healthy controls and one comparing the intestinal permeability in ESRD patients to healthy controls. RESULTS: From the 480 identified reports, 15 met our inclusion criteria. Methods that were used to assess the intestinal permeability varied from markers measured in plasma to methods based on calculating the urinary excretion of an orally administered test substance. None of the applied methods has been validated in CKD patients and the influence of decreased renal function on the different methods remains unclear to a certain extent. Methods that seem the least likely to be influenced by decreased renal function are the quantitative PCR (qPCR) for bacterial DNA in blood and D-lactate. Considering the results published by the included studies; the studies including patients with mild to moderate CKD conducted conflicting results. Some studies did report an increase in intestinal permeability whilst other did not find a significant increased permeability. However, despite the variety in used methods among the different studies, all studies measuring the intestinal permeability in ESRD point out a significant increased intestinal permeability. Results should nevertheless be interpreted with caution due to the possible influence of a decreased glomerular filtration rate on test results. CONCLUSION: The intestinal permeability in CKD: (1) could be measured by qPCR for bacterial DNA in blood and D-lactate; and (2) seems to be increased in ESRD.     

Biomarkers in chronic kidney disease,from kidney function to kidney damage

Chronic kidney disease(CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate(GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine(SCr) and cystatin C(Cys C). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associationswith disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 m L/min per 1.73 m2. Equations combining Cys C and SCr perform better than the equations using either Cys C or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, Cys C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.     

Baroreflex dysfunction in chronic kidney disease

Chronic kidney disease (CKD) patients have high cardiovascular mortality and morbidity. The presence of traditional and CKD related risk factors results in exaggerated vascular calcification in these patients. Vascular calcification is associated with reduced large arterial compliance and thus impaired baroreflex sensitivity (BRS) resulting in augmented blood pressure (BP) variability and hampered BP regulation. Baroreflex plays a vital role in short term regulation of BP. This review discusses the normal baroreflex physiology, methods to assess baroreflex function, its determinants along with the prognostic significance of assessing BRS in CKD patients, available literature on BRS in CKD patients and the probable patho-physiology of baroreflex dysfunction in CKD.     

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.     

慢性肾脏病伴慢性前列腺炎合并心理障碍患者的针对性护理干预效果分析

目的:探讨慢性肾脏病伴慢性前列腺炎患者心理障碍及相关干预措施。方法:慢性肾脏病伴慢性前列腺炎患者82例,分为对照组和实验组。对照组给予常规治疗和护理措施。实验组给予常规治疗和护理,同时给予针对性护理干预措施,必要时加用抗抑郁药治疗。结果:实验组总有效率97.56%高于对照组总有效率80.49%,差异具有统计学意义(P0.05)。干预后,实验组CPSI评分低于对照组CPSI评分,差异具有统计学意义(P0.05)。干预后,实验组QOL评分低于对照组QOL评分,差异有统计学意义(P0.01)。结论:在治疗方法一样的情况下,对慢性肾脏病伴慢性前列腺病人针对性的干预措施可明显提高患者的治愈率,改善患者生活质量和前列腺症状,具有较高的临床应用价值。     

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 end-stage-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.     

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.     

Frequent office visits of patients with chronic kidney disease: Is a prelude to prevention of dialysis

This study is an excerpt of broad-based office practice which is designed to treat patients with diabetes and hypertension, the two most common causes of chronic kidney disease (CKD), as well as CKD of unknown etiology. This model of office practice is dedicated to evaluating patients with CKD for their complete well-being; blood pressure control, fluid control and maintenance of acid-base status and hemoglobin. Frequent office visits, every four to six weeks, confer a healthy life style year after year associated with a feeling of good well-being and a positive outlook. Having gained that, such patients remain compliant to their medication and diet, and scheduled laboratory and office visits which are determinant of a dialysis-free life.     

Pre-treatment considerations in childhood hypertension due to chronic kidney disease

Hypertension(HTN) develops very early in childhood chronic kidney disease(CKD). It is linked with rapid progression of kidney disease, increased morbidity and mortality hence the imperative to start antihypertensive medication when blood pressure(BP)is persistently 90 th percentile for age, gender, and height in non-dialyzing hypertensive children with CKD. HTN pathomechanism in CKD is multifactorial and complexly interwoven. The patient with CKD-associated HTN needs to be carefully evaluated for co-morbidities that frequently alter the course of the disease as successful treatment of HTN in CKD goes beyond life style modification and anti-hypertensive therapy alone. Chronic anaemia, volume overload, endothelial dysfunction, arterial media calcification, and metabolic derangements like secondary hyperparathyroidism, hyperphosphataemia, and calcitriol deficiency are a few co-morbidities that may cause or worsen HTN in CKD. It is important to know if the HTN is caused or made worse by the toxic effects of medications like erythropoietin, cyclosporine, tacrolimus, corticosteroids and non-steroidal anti-inflammatory drugs. Poor treatment response may be due to any of these co-morbidities and medications. A satisfactory hypertensive CKD outcome, therefore, depends very much on identifying and managing these co-morbid conditions and HTN promoting medications promptly and appropriately. This review attempts to point attention to factors that may affect successful treatment of the hypertensive CKD child and how to attain the desired therapeutic BP target.